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Efficient, chemoselective synthesis of immunomicelles using single-domain antibodies with a C-terminal thioester
PubMed Central
Background Classical bioconjugation strategies for generating antibody-functionalized nanoparticles are non-specific and typically result in heterogeneous compounds that can be compromised in activity. Expression systems based on self-cleavable intein domains allow the generation of recombinant proteins with a C-terminal thioester, providing a unique handle for site-specific conjugation using native chemical ligation (NCL). However, current methods to generate antibody fragments with C-terminal thioesters require cumbersome refolding procedures, effectively preventing application of NCL for antibody-mediated targeting and molecular imaging. Results Targeting to the periplasm of E. coli allowed efficient production of correctly-folded single-domain antibody (sdAb)-intein fusions proteins. On column purification and 2-mercapthoethanesulfonic acid (MESNA)-induced cleavage yielded single-domain antibodies with a reactive C-terminal MESNA thioester in good yields. These thioester-functionalized single-domain antibodies allowed synthesis of immunomicelles via native chemical ligation in a single step. Conclusion A novel procedure was developed to obtain soluble, well-folded single-domain antibodies with reactive C-terminal thioesters in good yields. These proteins are promising building blocks for the chemoselective functionalization via NCL of a broad range of nanoparticle scaffolds, including micelles, liposomes and dendrimers.
Reulen, Sanne WA; van Baal, Ingrid; Raats, Jos MH; Merkx, Maarten
Ag\\/MCM-41 as a highly efficient mesostructured catalyst for the chemoselective synthesis of methyl glycolate and ethylene glycol
Microsoft Academic Search
A novel highly efficient heterogeneous Ag\\/MCM-41 catalyst was prepared by ammonia-evaporation deposition-precipitation method and displayed outstanding methyl glycolate (MG) selectivity (up to 99%) and ethylene glycol (EG) selectivity (up to 99%) in the chemoselective gas-phase hydrogenation of dimethyloxalate (DMO). Systematic characterizations have been carried out to elucidate the bulk and surface physicochemical properties of the catalysts. It is shown that
Anyuan Yin; Chao Wen; Wei-Lin Dai; Kangnian Fan
Chemoselective synthesis of oligosaccharides of 2-deoxy-2-aminosugars
Along with the application of the S-benzoxazolyl glycosides to the high-yielding synthesis of disaccharides of the 2-amino-2-deoxy series, chemoselective assembly of oligosaccharides containing multiple residues of 2-amino-2-deoxyglycoses is reported. This modified armed-disarmed approach is relying on the observation that 2-N-trichloroethoxycarbonyl derivatives of S-benzoxazolyl glycosides are significantly more reactive than their 2-N-phthaloyl counterparts in MeOTf-promoted glycosylations. This allowed efficient chemoselective synthesis of 1,2-trans-linked oligosaccharides, the disarmed reducing end of which can be activated for immediate second step glycosidation in the presence of a more powerful activator AgOTf. As a result of this two-step activation, trans-trans-patterned trisaccharides could be assembled in a highly efficient manner. This result differs from the classic armed-disarmed technique, according to which usually cis-trans-patterned oligosaccharides are generated.
Bongat, Aileen F. G.; Kamat, Medha N.; Demchenko, Alexei V.
A chemoselective oxidation of monosubstituted ethylene glycol: facile synthesis of optically active ?-hydroxy acids.
A mild and efficient method for the synthesis of optically active ?-hydroxy acids through chemoselective oxidation of monosubstituted ethylene glycols using the TEMPO-NaOCl reagent system is described. It is evident from our studies that the solvent, pH and reaction temperature are very crucial for the success of this oxidation. The versatility of this method has been demonstrated with a variety of aliphatic, aromatic and carbohydrate substrates bearing various functional groups. PMID:24850510
Chinthapally, Kiran; Baskaran, Sundarababu
Chemoselective synthesis of ketones and ketimines by addition of organometallic reagents to secondary amides.
The development of efficient and selective transformations is crucial in synthetic chemistry as it opens new possibilities in the total synthesis of complex molecules. Applying such reactions to the synthesis of ketones is of great importance, as this motif serves as a synthetic handle for the elaboration of numerous organic functionalities. In this context, we report a general and chemoselective method based on an activation/addition sequence on secondary amides allowing the controlled isolation of structurally diverse ketones and ketimines. The generation of a highly electrophilic imidoyl triflate intermediate was found to be pivotal in the observed exceptional functional group tolerance, allowing the facile addition of readily available Grignard and diorganozinc reagents to amides, and avoiding commonly observed over-addition or reduction side reactions. The methodology has been applied to the formal synthesis of analogues of the antineoplastic agent Bexarotene and to the rapid and efficient synthesis of unsymmetrical diketones in a one-pot procedure. PMID:22354438
Bechara, William S; Pelletier, Guillaume; Charette, Andr� B
Inverse-electron-demand Diels-Alder reaction as a highly efficient chemoselective ligation procedure: synthesis and function of a BioShuttle for temozolomide transport into prostate cancer cells.
Hormone-refractory prostate cancer (HRPC), insensitive to most cytostatic interventions, features low response rates and bad prognosis. Studies with HRPC treated with temozolomide (TMZ) showed a poor response and the results were discouraging. Therefore, TMZ has been considered to be ineffective for the treatment of patients with symptomatic and progressive HRPC. A solution to this problem is demonstrated in this study by combining proper solid-phase peptide synthesis and a chemoselective new 'click' chemistry based on the Diels-Alder reaction with 'inverse-electron-demand' (DAR(inv)) for the construction of a highly efficient TMZ-BioShuttle in which TMZ is ligated to transporter and subcellular address molecules. The transport to the targeted nuclei resulted in much higher efficiency and better pharmacological effects. The reformulation of TMZ to TMZ-BioShuttle achieved higher in vitro killing of prostate cancer cells. Accordingly, the potential of TMZ for the treatment of prostate tumors was dramatically enhanced even in a tenfold lower concentration than applied normally. This TMZ-BioShuttle may be well suited for combining chemotherapy with other cytostatic agents or radiation therapy. PMID:19177421
Pipkorn, R�diger; Waldeck, Waldemar; Didinger, Bernd; Koch, Mario; Mueller, Gabriele; Wiessler, Manfred; Braun, Klaus
Study on the total synthesis of velbanamine: Chemoselective dioxygenation of alkenes with PIFA via a stop-and-flow strategy
Summary A �stop-and-flow� strategy was developed for the chemoselective dioxygenation of alkenes with a PIFA-initiated cyclization. This method is conceived for the desymmetrization of seco-diene, and a series of substituted 5-hydroxymethyl-?-lactones were constructed after hydrolysis. This strategy also differentiates terminally substituted alkenes and constitutes a potentially novel synthetic approach for the efficient synthesis toward velbanamine.
Liu, Huili; Zheng, Kuan; Lu, Xiang
The Chemoselective Reduction of Isoxazoline ?-Lactams Through Iminium Aza-Diels-Alder Reactions: A Short-Cut Synthesis of Aminols as Valuable Intermediates towards Nucleoside Derivatives
Isoxazoline ?-lactams are prepared starting from the regioisomeric cycloadducts of benzonitrile oxide to the N-alkyl 2-azanorbornenes taking advantage of the efficient catalytic oxidation by RuO4. The reduction of the amide groups is easily conducted in the presence of LiAlH4 under mild conditions, which allowed for the chemoselective reduction of the amide moiety followed by ring opening to afford the desired conformationally locked isoxazoline-carbocyclic aminols, as valuable intermediates for nucleoside synthesis.
Memeo, Misal Giuseppe; Mella, Mariella; Quadrelli, Paolo
A powerful, practical and chemoselective synthesis of 2-anilinoalkanols catalyzed by Bi(TFA) 3 or Bi(OTf) 3 in the presence of molten TBAB
A facile and efficient synthesis of ?-amino alcohols by ring opening of epoxides with anilines in good to excellent yields in the presence of catalytic amounts of Bi(TFA)3 or Bi(OTf)3 via the use of molten tetrabutylammonium bromide (TBAB) as an ionic liquid is described. In addition, the observed chemoselectivity can be considered as a noteworthy advantage of this method.
Mohammd M. Khodaei; Ahmad R. Khosropour; Kazem Ghozati
Highly efficient and chemoselective ?-iodination of acrylate esters through Morita-Baylis-Hillman-type chemistry.
The chemoselective ?-iodination of various simple and multi-functionalised acrylic esters is efficiently accomplished by a Morita-Baylis-Hillman protocol involving the use of N-iodophthalimide, 3-quinuclidinol and KF-Celite in acetonitrile. No degradation of the obtained compounds was observed under the optimized conditions thus, furnishing ?-iodoacrylates suitable for organometallic reactions (i.e. Nozaki-Kishi-Hiyama type coupling). PMID:23303274
Pace, Vittorio; Vilkauskait?, Gyt?; �a?kus, Algirdas; Holzer, Wolfgang
Transfer hydrogenation using recyclable polyurea-encapsulated palladium: efficient and chemoselective reduction of aryl ketones.
A robust and recyclable palladium catalyst [Pd0EnCat] has been prepared by ligand exchange of polyurea-encapsulated palladium(II) acetate with formic acid, resulting in deposition of Pd(0) in the support material; Pd0EnCat is shown to be a highly efficient transfer hydrogenation catalyst for chemoselective reduction of a wide range of aryl ketones to benzyl alcohols. PMID:12703769
Yu, Jin-Quan; Wu, Hai-Chen; Ramarao, Chandrashekar; Spencer, Jonathan B; Ley, Steven V
How the Arming Participating Moieties can Broaden the Scope of Chemoselective Oligosaccharide Synthesis by Allowing the Inverse Armed-Disarmed Approach
A new method for stereocontrolled glycosylation and chemoselective oligosaccharide synthesis has been developed. It has been determined that complete 1,2-trans selectivity can be achieved with the use of a 2-O-picolyl moiety, a novel neighboring group that is capable of efficient participation via a six-membered intermediate. The application of the picolyl concept to glycosidations of thioimidoyl, thioglycosyl, and trichloroacetimidoyl glycosyl donors is demonstrated. The picolyl moiety also retains the glycosyl donor in the armed state, as opposed to conventional acyl participating moieties. We name this new approach - �inverse armed-disarmed� strategy, because it allows for the chemoselective introduction of a 1,2-trans glycosidic linkage prior to other linkages. In the context of the oligosaccharide synthesis, the strategy provides trans-trans and trans-cis patterned oligosaccharides as opposed to classic Fraser-Reid�s armed-disarmed approach leading to cis-trans and cis-cis linkages.
Smoot, James T.; Demchenko, Alexei V.
A convergent stereoselective synthesis of quinolizidines and indolizidines: chemoselective coupling of 2-hydroxymethyl-substituted allylic silanes with imines.
A convergent synthesis of stereodefined indolizidines and quinolizidines through chemoselective allyl transfer between 2-hydroxymethyl-substituted allylic silanes and imines is described. Overall, highly substituted heterocycles that contain three stereogenic centers and up to four fused rings can be accessed in two steps from relatively simple coupling partners. PMID:19950989
Yang, Dexi; Micalizio, Glenn C
A Convergent Stereoselective Synthesis of Quinolizidines and Indolizidines: Chemoselective Coupling of 2-Hydroxymethyl Substituted Allylic Silanes with Imines
A convergent synthesis of stereodefined indolizidines and quinolizidines is described through chemoselective allyltransfer between 2-hydroxymethyl substituted allylic silanes and imines. Overall, highly substituted heterocycles that contain three stereogenic centers and up to four fused rings are accessed in two steps from relatively simple coupling partners.
Yang, Dexi; Micalizio, Glenn C.
Chemoselective ligation
The present invention features a chemoselective ligation reaction that can be carried out under physiological conditions. In general, the invention involves condensation of a specifically engineered phosphine, which can provide for formation of an amide bond between the two reactive partners resulting in a final product comprising a phosphine moiety, or which can be engineered to comprise a cleavable linker so that a substituent of the phosphine is transferred to the azide, releasing an oxidized phosphine byproduct and producing a native amide bond in the final product. The selectivity of the reaction and its compatibility with aqueous environments provides for its application in vivo (e.g., on the cell surface or intracellularly) and in vitro (e.g., synthesis of peptides and other polymers, production of modified (e.g., labeled) amino acids).
Saxon, Eliana (Albany, CA); Bertozzi, Carolyn R. (Berkeley, CA)
Saxon, Eliana (Albany, CA); Bertozzi, Carolyn Ruth (Berkeley, CA)
Saxon, Eliana (Albany, CA); Bertozzi, Carolyn (Berkeley, CA)
The present invention features a chemoselective ligation reaction that can be carried out under physiological conditions. In general, the invention involves condensation of a specifically engineered phosphine, which can provide for formation of an amide bond between the two reactive partners resulting in a final product comprising a phosphine moiety, or which can be engineered to comprise a cleavable linker so that a substituent of the phosphine is transferred to the azide, releasing an oxidized phosphine byproduct and producing a native amide bond in the final product. The selectivity of the reaction and its compatibility with aqueous environments provides for its application in vivo (e.g. on the cell surface or intracellularly) and in vitro (e.g., synthesis of peptides and other polymers, production of modified (e.g., labeled) amino acids).
Selective synthesis of Rh5 carbonyl clusters within a polyamine dendrimer for chemoselective reduction of nitro aromatics.
The selective synthesis of the [Rh5(CO)15](-) cluster within the PPI dendrimer was successfully demonstrated. The dendrimer-encapsulated [Rh5(CO)15](-) was resistant to decomposition under the catalytic reaction conditions and exhibited extremely high selectivity for the chemoselective reduction of nitro groups of various nitro aromatics with other reducible groups using CO/H2O as a reductant. PMID:24819549
Maeno, Zen; Mitsudome, Takato; Mizugaki, Tomoo; Jitsukawa, Koichiro; Kaneda, Kiyotomi
Chemoselective synthesis of substituted pyrazoles through AgOTf-catalyzed cascade propargylic substitution-cyclization-aromatization.
A cascade AgOTf-catalyzed chemoselective approach to 3,5/1,3-disubstitued pyrazoles from propargylic alcohols and para-tolylsulfonohydrazide has been developed. Good chemoselectivity is observed depending on the different substituents in the alkyne moiety of the propargylic alcohols, generating two different kinds of products through different aromatization mechanisms. The pyrazolo[5,1-a]isoquinoline skeleton can also be effectively constructed by this method through a cascade bicyclization process. PMID:23188378
Xu, Su-Xia; Hao, Lu; Wang, Tao; Ding, Zong-Cang; Zhan, Zhuang-Ping
Chemoselective alcoholysis/acetolysis of trans-ketals over cis-ketals and its application in the total synthesis of the cellular second messenger, D-myo-inositol-1,4,5-trisphosphate.
The involvement of natural phosphoinositols in various cellular signalling processes and the use of synthetic inositol derivatives in catalysis, supramolecular chemistry, natural product synthesis etc. gave momentum to myo-inositol chemistry. The presence of six secondary hydroxyl groups necessitates efficient protection-deprotection strategies for the synthesis of inositol derivatives. An important strategy for the initial protection of myo-inositol is the di-ketalization, which gives a mixture of three diketals, each having both cis-fused and trans-fused ketals. It is important to have methodologies either to selectively hydrolyze one of the two ketals or to convert one of the two acid labile ketals to an orthogonal base labile protecting group. By exploiting the difference in strain between trans-ketals and cis-ketals, we developed two operationally simple, high yielding methodologies for the chemoselective hydrolysis/acetolysis of trans-ketals (both isopropylidene and cyclohexylidene) of inositols, leaving the cis-ketal undisturbed, using cheap and easily preparable H2SO4-silica as the catalyst. Also, terminal ketal moieties of carbohydrates and acyclic polyols could be selectively hydrolyzed/acetolyzed leaving the internal ketals intact. The use of methanol as the solvent leads to chemoselective alcoholysis but the use of DCM and acetic anhydride leads to chemoselective acetolysis. Applying this methodology, a short synthesis of D-myo-inositol-1,4,5-trisphosphate has been achieved. PMID:23851711
Vidyasagar, Adiyala; Pathigoolla, Atchutarao; Sureshan, Kana M
Using Nazarov Electrocyclization to Stage Chemoselective [1,2]-Migrations: Stereoselective Synthesis of Functionalized Cyclopentenones
Highly functionalized cyclopentenones are prepared stereospecifically based on a chemoselective copper(II)-mediated Nazarov/Wagner-Meerwein rearrangement sequence. After the initial 4? electrocyclization, this reaction involves two sequential [1,2]-migrations depending upon both migratory ability and steric bulk of the substituents at C1 and C5. This sequence can be achieved by using a catalytic quantity of copper(II) in combination with a weak Lewis acid. The mechanism of the reaction is also supported by DFT computations.
Leboeuf, David; Huang, Jie; Gandon, Vincent
Reagent control of [1,2]-Wagner-Meerwein shift chemoselectivity following the Nazarov cyclization: application to the total synthesis of enokipodin B.
An approach toward the carbon framework of various sesquiterpenes from the herbertane and cuparane families is described, including the concise total synthesis of enokipodin B. The key step is the construction of the vicinal quarternary centers of the skeleton through a tandem Nazarov cyclization/Wagner-Meerwein rearrangement mediated by a copper(II) complex. During this study, it was also found that changing the ligand architecture on the copper(II) promoter improved the chemoselectivity of the cationic rearrangement. PMID:23436444
Leb�uf, David; Wright, Christopher M; Frontier, Alison J
Oxyhomologues of anandamide and related endolipids: chemoselective synthesis and biological activity.
The three amide oxyhomologues of the endolipids N-arachidonoylethanolamine (anandamide, AEA, 1a), N-oleoylethanolamine (OEA, 2a), and N-palmitoylethanolamine (PEA, 3a) have been prepared in a chemoselective way, capitalizing on the easy availability of O-[2-(triisopropylsilyoxy)ethyl]hydroxylamine (6) and the surprising complementary selectivity observed in the acylation of N-[2-(tert-butyldiphenylsilyloxy)ethyl]hydroxylamine (7) with the PPAA and the DCC/HOBT protocols. Reversal of the cannabinoid CB(1)/CB(2) receptor affinity ratio was observed for the first time in a derivative of anandamide (the O-alkyl-N-acyl hydroxylamine 1b), while the other oxyhomologues (1c and 1d) showed only marginal cannabimimetic activity. Compounds with unsaturated acyl chains generally retained vanilloid activity and showed an increased stability toward FAAH compared to their corresponding ethanolamides. Taken together, these observation show that oxyhomologation has a pronounced effect on both the pharmacodynamic and the pharmacokinetic properties of endogenous ethanolamides, suggesting a general relevance of this maneuver for the modification of amide pharmacophores. PMID:16570929
Appendino, Giovanni; Minassi, Alberto; Berton, Luca; Moriello, Aniello Schiano; Cascio, Maria Grazia; De Petrocellis, Luciano; Di Marzo, Vincenzo
Organocatalysed synthesis of isoxazolines initiated by a chemoselective oxa-Michael reaction of N-BocNHOH.
An organocatalysed and chemoselective one-pot oxa-Michael-cyclocondensation reaction of N-BocNHOH to unsaturated ?-ketoesters is reported which affords an original entry to enantioenriched 3-isoxazoline carboxylate derivatives as biorelevant heterocyclic frameworks. PMID:24414044
No�l, R; Gembus, V; Levacher, V; Bri�re, J-F
Chemoselective approaches to glycoprotein assembly
SciTech Connect
Oligosaccharides on proteins and lipids play central roles in human health and disease. The molecular analysis of glycoconjugate function has benefited tremendously from new methods for their chemical synthesis, which provides homogeneous material not attainable from biosynthetic systems. Still, glycoconjugate synthesis requires the manipulation of multiple stereocenters and protecting groups and remains the domain of a few expert laboratories around the world. This account summarizes chemoselective approaches for assembling homogeneous glycoconjugates that attempt to reduce the barriers to their synthesis. The objective of these methods is to make glycoconjugate synthesis accessible to a broader community, thereby accelerating progress in glycobiology.
Hang, Howard C.; Bertozzi, Carolyn R.
Direct carbon-carbon bond formation via chemoselective soft enolization of thioesters: a remarkably simple and versatile crossed-Claisen reaction applied to the synthesis of LY294002.
Thioesters undergo chemoselective soft enolization and acylation by N-acylbenzotriazoles on treatment with MgBr2 x OEt2 and i-Pr2NEt to give beta-keto thioesters. Prior enolate formation is not required, and the reaction is conducted using untreated CH2Cl2 open to the air. The coupled products are stable synthetic equivalents of beta-keto acids and can be converted directly into beta-keto esters, beta-keto amides, and beta-diketones under mild conditions. The utility of this carbon-carbon bond-forming method is shown through the synthesis of the PI3-K inhibitor LY294002. PMID:18681454
Zhou, Guoqiang; Lim, Daniel; Coltart, Don M
EPA Science Inventory
A simple, facile, and chemoselective N-benzyloxycarbonylation of amines using silica-sulfuric acid that proceeds under solvent-free conditions at room temperature has been achieved. These reactions are applicable to a wide variety of primary (aliphatic, cyclic) secondary amines, ...
Synthesis of novel 2-deoxy-?-benzyl-C-glycosides by highly stereo- and chemoselective hydrogenation of exo-glycals.
Novel 2-deoxy-?-benzyl-C-glycosides were prepared in good yields and excellent stereoselectivity by a route involving the Wittig reaction of glycosyl phosphonium salts and reduction of exo-glycals as key steps. Hydrogenation of benzyl protected enol ethers was performed with Pd/C(en) as an effective chemoselective catalyst to afford exclusively ? anomers. PMID:24887703
D�az, Gisela; Ponzinibbio, Agust�n; Bravo, Rodolfo Daniel
Reaction of Corey Ylide with ?,?-Unsaturated Ketones: Tuning of Chemoselectivity toward Dihydrofuran Synthesis.
A straightforward, efficient, and reliable approach to synthetically valuable 2,3-dihydrofurans via a reaction between Corey ylide and ?,?-unsaturated ketones has been developed. The use of simple and widely spread starting materials as well as mild reaction conditions and scalability provide a broad scope of 2,3-dihydrofurans. PMID:24819312
Chagarovsky, Alexey O; Budynina, Ekaterina M; Ivanova, Olga A; Villemson, Elena V; Rybakov, Victor B; Trushkov, Igor V; Melnikov, Mikhail Ya
Chemoselective Hydroxyl Group Transformation: An Elusive Target�
The selective reaction of one functional group in the presence of others is not a trivial task. A noteworthy amount of research has been dedicated to the chemoselective reaction of the hydroxyl moiety. This group is prevalent in many biologically important molecules including natural products and proteins. However, targeting the hydroxyl group is difficult for many reasons including its relatively low nucleophilicity in comparison to other ubiquitous functional groups such as amines and thiols. Additionally, many of the developed chemoselective reactions cannot be used in the presence of water. Despite these complications, chemoselective transformation of the hydroxyl moiety has been utilized in the synthesis of complex natural product derivatives, the reaction of tyrosine residues in proteins, the isolation of natural products and is the mechanism of action of myriad drugs. Here, methods for selective targeting of this group, as well as applications of several devised methods, are described.
Trader, Darci J.; Carlson, Erin E.
Chemoselective hydroxyl group transformation: an elusive target.
The selective reaction of one functional group in the presence of others is not a trivial task. A noteworthy amount of research has been dedicated to the chemoselective reaction of the hydroxyl moiety. This group is prevalent in many biologically important molecules including natural products and proteins. However, targeting the hydroxyl group is difficult for many reasons including its relatively low nucleophilicity in comparison to other ubiquitous functional groups such as amines and thiols. Additionally, many of the developed chemoselective reactions cannot be used in the presence of water. Despite these complications, chemoselective transformation of the hydroxyl moiety has been utilized in the synthesis of complex natural product derivatives, the reaction of tyrosine residues in proteins, the isolation of natural products and is the mechanism of action of myriad drugs. Here, methods for selective targeting of this group, as well as applications of several devised methods, are described. PMID:22695722
Trader, Darci J; Carlson, Erin E
Chemoselective Attachment of Biologically Active Proteins to Surfaces by Native Chemical Ligation
The present work describes our ongoing efforts towards the creation of micro and nanoscaled ordered arrays of protein covalently attached to site-specific chemical linkers patterned by different microlithographic techniques. We present a new and efficient solid-phase approach for the synthesis of chemically modified long alkyl-thiols. These compounds can be used to introduce chemoselective reacting groups onto silicon-based surfaces. We show that these modified thiols can be used for creating nano- and micrometric chemical patterns by using different lithographic techniques. We show that these patterns can react chemoselectively with proteins which have been recombinantly modified to contain complementary chemical groups at specific positions thus resulting in the oriented attachment of the protein to the surface.
Cheung, C L; de Yoreo, J J; Coleman, M; Camarero, J A
Assembly of Oriented Virus Arrays by Chemo-Selective Ligation Methods and Nanolithography Techniques
The present work describes our ongoing efforts towards the creation of nano-scaled ordered arrays of protein/virus covalently attached to site-specific chemical linkers patterned by different nanolithograpy techniques. We will present a new and efficient solid-phase approach for the synthesis of chemically modified long alkyl-thiols. These compounds can be used to introduce chemoselective reacting groups onto gold and silicon-based surfaces. Furthermore, these modified thiols have been used to create nanometric patterns by using different nanolithography techniques. We will show that these patterns can react chemoselectively with proteins and/or virus which have been chemically or recombinantly modified to contain complementary chemical groups at specific positions thus resulting in the oriented attachment of the protein or virus to the surface.
Camarero, J A; Cheung, C L; Lin, T; Johnson, J E; Weeks, B L; Noy, A; De Yoreo, J J
Chemoselective hydrosilylation of hydroxyketones
A chemoselective method for the hydrosilylation of ketones has been developed, using the combination of triphenylsilane and a catalyst prepared from Ni(COD)2 and the simple N-heterocyclic carbene IMes. The most notable feature of this method is that free hydroxyls are largely unaffected, thus providing a simple one-step procedure for the conversion of hydroxyketones to mono-protected diols, wherein the protecting group is exclusively installed on the ketone-derived hydroxyl. The process is typically high yielding with both simple ketones and more complex hydroxyketone substrates.
Lage, Marta L.; Bader, Scott J.; Sa-ei, Kanicha; Montgomery, John
A Mild and Efficient Chemoselective Tetrahydropyranylation of Alcohols Using Bronsted Acidic Ionic Liquid as Catalyst Under Solvent-Free Conditions
A straightforward and efficient method for preparation of morpholinium bisulfate ([mroH] HSO4) as a novel acidic IL is reported. The application of this efficient and inexpensive acidic ionic liquid catalyst for tetrahydropyranylation of alcohols under mild and solvent-free conditions at room was investigated.
Abdol R. Hajipour; Zahra. Nasresfahani
Mild and Efficient Chemoselective Tetrahydropyranylation of Alcohols Using Br�nsted Acidic Ionic Liquid as Catalyst Under Solvent-Free Conditions
A straightforward and efficient method for preparation of morpholinium bisulfate ([mroH]HSO4) as a novel acidic ionic liquid is reported. The application of this efficient and inexpensive acidic ionic liquid catalyst for tetrahydropyranylation of alcohols under mild and solvent-free conditions at room was investigated.
Abdol R. Hajipour; Zahra Nasresfahani
BACKGROUND: Classical bioconjugation strategies for generating antibody-functionalized nanoparticles are non-specific and typically result in heterogeneous compounds that can be compromised in activity. Expression systems based on self-cleavable intein domains allow the generation of recombinant proteins with a C-terminal thioester, providing a unique handle for site-specific conjugation using native chemical ligation (NCL). However, current methods to generate antibody fragments with C-terminal
Sanne W. A. Reulen; Ingrid van Baal; Jos M. H. Raats; Maarten Merkx
Aminocyanation by the addition of N-CN bonds to arynes: chemoselective synthesis of 1,2-bifunctional aminobenzonitriles.
An efficient aminocyanation by the direct addition of aryl cyanamides to arynes is described, enabling incorporation of highly useful amino and cyano groups synchronously via cleavage of inert N-CN bonds, affording synthetically useful 1,2-bifunctional aminobenzonitriles. The postsynthetic functionalization of the aminocyanation products allows diverse formation of synthetically important derivatives such as drug molecule Ponstan and fused heterocycles. PMID:24325782
Rao, Bin; Zeng, Xiaoming
Chemoselective CaO-mediated acylation of alcohols and amines in 2-methyltetrahydrofuran.
Calcium oxide is proposed as an innocuous acid scavenger for the chemoselective synthesis of amide- and ester-type compounds. Although these molecules have wide spread applications in organic and pharmaceutical chemistry, and a large number of routes have been designed for their synthesis, the development of more efficient and environmentally friendly acylation strategies remains an ongoing challenge. The use of CaO allows for the stoichiometric acylation of primary alcohols in the presence of phenols or tertiary alcohols; amines can also be subjected to acylation reactions in the presence of hydroxyl groups. Chirality is obtained through acylation if the starting material is an optically pure alcohol or if a chiral acylating agent is used. Furthermore, the use of 2-methyltetrahydrofuran (2-MeTHF), a more ecofriendly solvent, leads to maximized yields. This protocol is successfully applied to the synthesis of an interesting N-aryloxazolidin-2-one intermediate for the preparation of linezolid-type compounds. PMID:23532956
Pace, Vittorio; Hoyos, Pilar; Alc�ntara, Andr�s R; Holzer, Wolfgang
Chemoselective Tetrahydropyranylation of Alcohols and Their Detetrahydropyranylation Using Silicasulphuric Acid as a Reusable Catalyst
A simple, mild, and efficient protocol for chemoselective protection of alcohols over phenols as tetrahydropyranyl ethers and their deprotection using silicasulphuric acid as a reusable solid acid catalyst is described.
D. M. Pore; Uday V. Desai; R. B. Mane; P. P. Wadgaonkar
Chemoselective Intermolecular ?-Arylation of Amides.
A new approach for the fully chemoselective ?-arylation of amides is presented. By means of electrophilic amide activation, aryl groups can be regioselectively introduced ?- to amides, even in the presence of esters and alkyl ketones. Mechanistic studies reveal key reaction intermediates and emphasize a remarkably subtle base effect in this transformation. PMID:24740762
Peng, Bo; Geerdink, Danny; Far�s, Christophe; Maulide, Nuno
Prebiotically plausible oligoribonucleotide ligation facilitated by chemoselective acetylation
NASA Astrophysics Data System (ADS)
The recent synthesis of pyrimidine ribonucleoside-2?,3?-cyclic phosphates under prebiotically plausible conditions has strengthened the case for the involvement of ribonucleic acid (RNA) at an early stage in the origin of life. However, a prebiotic conversion of these weakly activated monomers, and their purine counterparts, to the 3?,5?-linked RNA polymers of extant biochemistry has been lacking (previous attempts led only to short oligomers with mixed linkages). Here we show that the 2?-hydroxyl group of oligoribonucleotide-3?-phosphates can be chemoselectively acetylated in water under prebiotically credible conditions, which allows rapid and efficient template-directed ligation. The 2?-O-acetyl group at the ligation junction of the product RNA strand can be removed under conditions that leave the internucleotide bonds intact. Remarkably, acetylation of mixed oligomers that possess either 2?- or 3?-terminal phosphates is selective for the 2?-hydroxyl group of the latter. This newly discovered chemistry thus suggests a prebiotic route from ribonucleoside-2?,3?-cyclic phosphates to predominantly 3?,5?-linked RNA via partially 2?-O-acetylated RNA.
Bowler, Frank R.; Chan, Christopher K. W.; Duffy, Colm D.; Gerland, B�atrice; Islam, Saidul; Powner, Matthew W.; Sutherland, John D.; Xu, Jianfeng
The recent synthesis of pyrimidine ribonucleoside-2?,3?-cyclic phosphates under prebiotically plausible conditions has strengthened the case for the involvement of RNA at an early stage in the origin of life. However, a prebiotic conversion of these weakly activated monomers, and their purine counterparts, to the 3?,5?-linked RNA polymers of extant biochemistry has been lacking � previous attempts leading only to short oligomers with mixed linkages. Here we show that the 2?-hydroxyl group of oligoribonucleotide-3?-phosphates can be chemoselectively acetylated in water under prebiotically credible conditions, allowing rapid and efficient template-directed ligation. The 2?-O-acetyl group at the ligation junction of the product RNA strand can be removed under conditions that leave the internucleotide bonds intact. Remarkably, acetylation of mixed oligomers possessing either 2?- or 3?-terminal phosphates is selective for the 2?-hydroxyl group of the latter. This newly discovered chemistry thus suggests a prebiotic route from ribonucleoside-2?,3?-cyclic phosphates to predominantly 3?,5?-linked RNA via partially 2?-O-acetylated-RNA.
Bowler, Frank R.; Chan, Christopher K. W.; Duffy, Colm D.; Gerland, Beatrice; Islam, Saidul; Powner, Matthew W.; Sutherland, John D.; Xu, Jianfeng
Cesium Carbonate Catalyzed Chemoselective Hydrosilylation of Aldehydes and Ketones under Solvent-Free Conditions.
Cs2 CO3 has been found to be an efficient and chemoselective catalyst for reduction of aldehydes and ketones to alcohols with one equivalent of Ph2 SiH2 as the reductant under solvent-free conditions. Most of the aldehydes employed can be effectively hydrosilated quantitatively to give the corresponding silyl ethers in 2?h at room temperature, whereas the hydrosilylation of ketones proceeded smoothly at 80?�C. The catalyst system tolerates a number of functional groups including halogen, alkoxyl, olefin, ester, nitro, cyano, and heteroaromatic groups; the selective hydrosilylation of aldehydes in the presence of ketone can be effectively controlled by temperature; and hydrosilylation of ?,?-unsaturated carbonyls resulted in the 1,2-addition products. The catalytic hydrosilylation of suitable dicarbonyls can be applied to the synthesis of poly(silyl ether)s with a high molecular weight and narrow molecular distribution. PMID:24989934
Zhao, Mengdi; Xie, Weilong; Cui, Chunming
Chemoselective Reactions of Citral: Green Syntheses of Natural Perfumes for the Undergraduate Organic Laboratory
ERIC Educational Resources Information Center
Chemoselectivity is a central concept in organic synthesis and may be readily appreciated in the context of the fragrant, polyfunctional natural product citral. We describe three single-step reactions students may perform on citral to synthesize other natural perfumes: citronellal, geraniol, nerol, or epoxycitral. Each of the reactions uses a�
Cunningham, Anna D.; Ham, Eun Y.; Vosburg, David A.
Direct, regioselective, and chemoselective preparation of novel boronated tryptophans by Friedel-Crafts alkylation.
A facile synthetic approach to the direct preparation of various novel unnatural boronated protected tryptophans using a regio- and chemoselective electrophilic substitution of 4- and 5-boronated indoles with N-protected dehydroalanine is described. The gram-scale synthesis of two free tryptophan boronic acids is also reported. PMID:22208950
Bartolucci, Silvia; Bartoccini, Francesca; Righi, Marika; Piersanti, Giovanni
A mild and efficient method for preparation of azides from alcohols using acidic ionic liquid [H-NMP]HSO 4
We report here an efficient method for the synthesis and characterization of [H-NMP]HSO4 and its application as an efficient catalyst and solvent for preparation of azides from corresponding alcohols under mild conditions. This processor showed high chemoselectivity for conversion of various alcohols to their corresponding azides.
Abdol R. Hajipour; Asiyeh Rajaei; Arnold E. Ruoho
A phosphate tether-mediated, one-pot, sequential ring-closing metathesis/cross-metathesis/chemoselective hydrogenation protocol.
A versatile three-step, one-pot, sequential reaction protocol involving ring-closing metathesis, cross-metathesis, and chemoselective hydrogenation is reported. This phosphate tether-mediated process occurs without intermediate isolation, is chemoselective, and is governed by stereoelectronic properties innate to phosphate tethers, which ultimately act to preserve the integrity of the bisallylic, bicyclic phosphate for subsequent nucleophilic additions. Overall, this process can be used to efficiently generate advanced polyol synthons. PMID:22568560
Venukadasula, Phanindra K M; Chegondi, Rambabu; Suryn, Gregory M; Hanson, Paul R
Sensing ionic liquids for chemoselective detection of acyclic and cyclic ketone gases.
Based on specific chemical reactions carried out at ambient temperature, an ultrasensitive and chemoselective measurement of both acyclic and cyclic ketone gases, such as acetone (a disease biomarker) and cyclohexanone (a signature chemical emanating from C-4 plastic explosives), in real time was efficiently achieved on QCM chips thin-coated with sensing ionic liquids. PMID:23422956
Liu, Yen-Liang; Tseng, Ming-Chung; Chu, Yen-Ho
Atom-economical chemoselective synthesis of 1,4-enynes from terminal alkenes and propargylic alcohols catalyzed by Cu(OTf)2.
A novel and efficient Cu(OTf)2-catalyzed sp(3)-sp(2) C-C bond formation reaction through the direct coupling of propargylic alcohols with terminal alkenes has been realized under mild conditions. The reaction is tolerant to air and is atom-economical, in accordance with the concept of modern green chemistry. The present protocol provides an attractive approach to a diverse range of 1,4-enynes in high to excellent yields. PMID:23379769
Huang, Guo-Bao; Wang, Xu; Pan, Ying-Ming; Wang, Heng-Shan; Yao, Gui-Yang; Zhang, Ye
Efficient Synthesis of 2Ethoxycarbonyl Indoles
An efficient one-pot procedure for the synthesis of 2-ethoxycarbonyl indoles from commercially available materials has been developed. The one-step procedure involves in situ formation of the hydrazones from phenylhydrazine hydrochloride and ethyl pyruvate in the presence of bismuth nitrate followed by Fischer cyclization in polyphosphoric acid and ethanol. This method is efficient and simple.
A. Sudhakara; H. Jayadevappa; K. M. Mahadevan; Vijaykumar Hulikal
Domino alkylation/oxa-Michael of 1,3-cyclohexanediones: steering the C/O-chemoselectivity to reach tetrahydrobenzofuranones.
An unprecedented domino synthesis of tetrahydrobenzofuran-4-ones is described implicating chemoselective alkylation of various 1,3-cyclohexanediones with bromocrotonate or crotonitrile followed by oxa-Michael cyclization. Further transformations of this core to reach molecular diversity are also presented. PMID:21826296
Devi, Rema B; Henrot, Matthias; De Paolis, Micha�l; Maddaluno, Jacques
Chemoselective Staudinger-phosphite reaction of symmetrical glycosyl-phosphites with azido-peptides and polygycerols.
In this paper we present the synthesis of glyco-phosphoramidate conjugates as easily accessible analogs of glyco-phosphorous esters via the Staudinger-phosphite reaction. This protocol takes advantage of synthetically accessible symmetrical carbohydrate phosphites in good overall yields, in which ethylene or propylene linkers can be introduced between phosphorous and galactose or lactose moieties. The phosphites were finally applied for the chemoselective reaction with azido-peptides and polyazido(poly)glycerols. PMID:22688846
B�hrsch, Verena; Mathew, Thresen; Zieringer, Maximilian; Vall�e, M Robert J; Artner, Lukas M; Dernedde, Jens; Haag, Rainer; Hackenberger, Christian P R
Palladium-catalyzed chemoselective decarboxylative ortho acylation of benzoic acids with ?-oxocarboxylic acids.
Palladium-catalyzed chemoselective decarboxylative cross coupling of benzoic acids with ?-oxocarboxylic acids was realized via an arene sp(2) C-H functionalization process. This work represents the first example of transition-metal-catalyzed cross-coupling reactions with two acids acting in different roles. The synthetic utility of this method was confirmed by the synthesis of pitofenone, an antispasmodic used in the combined drug Spasmalgon. PMID:23721458
Miao, Jinmin; Ge, Haibo
Chemoselective Nitration of Phenols with tert-Butyl Nitrite in Solution and on Solid Support
tert-Butyl nitrite was identified as a safe and chemoselective nitrating agent that provides preferentially mononitro derivatives of phenolic substrates in the presence of potentially competitive functional groups. On the basis of our control experiments, we propose that the reaction proceeds through the formation of O-nitrosyl intermediates prior to C-nitration via homolysis and oxidation. The reported nitration method is compatible with tyrosine-containing peptides on solid support in the synthesis of fluorogenic substrates for characterization of proteases.
Koley, Dipankar; Colon, Olvia C.; Savinov, Sergey N
Superarmed and Superdisarmed Building Blocks in Expeditious Oligosaccharide Synthesis
Traditional strategies for oligosaccharide synthesis often require extensive protecting and/or leaving group manipulations between each glycosylation step, thereby increasing the total number of synthetic steps while decreasing both the efficiency and yield. In contrast, expeditious strategies allow for the rapid chemical synthesis of complex carbohydrates by minimizing extraneous chemical manipulations. The armed�disarmed approach for chemoselective oligosaccharide synthesis is one such strategy that addresses these challenges. Herein, the significant improvements that have recently emerged in the area of chemoselective activation are discussed. These advancements have expanded the scope of the armed�disarmed methodology so that it can now be applied to a wider range of oligosaccharide sequences, in comparison to the original concept. Surveyed in this chapter are representative examples wherein these excellent innovations have already been applied to the synthesis of various oligosaccharides and glycoconjugates.
Premathilake, Hemali D.
An efficient total synthesis of (-)-huperzine A.
The total synthesis of Lycopodium alkaloid (-)-huperzine A has been accomplished in 10 steps with 17% overall yield from commercially abundant (R)-pulegone. The synthetic route features an efficient synthesis of 4 via a Buchwald-Hartwig coupling reaction, a dianion-mediated highly stereoselective alkylation of 4, and a rare example of an intramolecular Heck reaction of an enamine-type substrate. The stereoselective ?-elimination and the accompanying Wagner-Meerwein rearrangement are of particular interest. PMID:22900755
Ding, Rui; Sun, Bing-Feng; Lin, Guo-Qiang
Chemoselective and Enantioselective Oxidation of Indoles Employing Aspartyl Peptide Catalysts
Catalytic enantioselective indole oxidation is a process of particular relevance to the chemistry of complex alkaloids, as it has been implicated in their biosynthesis. In the context of synthetic methodology, catalytic enantioselective indole oxidation allows a rapid and biomimetic entry into several classes of alkaloid natural products. Despite this potentially high utility in the total synthesis, reports of catalytic enantioselective indole oxidation remain sparse. Here we report a highly chemoselective catalytic system for the indole oxidation that delivers 3-hydroxy-indolenines with good chemical yields and moderate to high levels of enantio- and diastereoselectivity (up to 95:5 er and up to 92:8 dr. These results represent, to our knowledge, the most selective values yet reported in the literature for catalytic asymmetric indole oxidation). Furthermore, the utility of enantioenriched hydroxy-indolenines in stereospecific rearrangements is demonstrated.
Kolundzic, Filip; Noshi, Mohammad N.; Tjandra, Meiliana; Movassaghi, Mohammad; Miller, Scott J.
Total Synthesis of Bryostatins. Development of Methodology for Atom-Economic and Stereoselective Synthesis of the C-ring Subunit
Bryostatins, a family of structurally complicated macrolides, exhibit an exceptional range of biological activities. The limited availability and structural complexity of these molecules makes development of an efficient total synthesis particularly important. This article describes our initial efforts towards the total synthesis of bryostatins, in which chemoselective and atom-economical methods for stereoselective assembly of the C-ring subunit were developed. A Pd-catalyzed tandem alkyne-alkyne coupling/6-endo-dig cyclization sequence was explored and successfully pursued in the synthesis of a dihydropyran ring system. Elaboration of this methodology ultimately led to a concise synthesis of the C-ring subunit of bryostatins.
Trost, Barry M.; Frontier, Alison J.; Thiel, Oliver R.; Yang, Hanbiao; Dong, Guangbin
Efficient Synthesis of Fluorescent Squaraine Rotaxane Dendrimers
A squaraine rotaxane scaffold with four alkynes groups is readily converted into a range of dendritic architectures using high yielding copper catalyzed alkyne azide cycloaddition (CuAAC) chemistry. A convergent synthesis approach is more efficient than a divergent pathway. Dendritic squaraine rotaxanes with peripheral amine groups can be further functionalized to produce multivalent deep-red fluorescent derivatives that exhibit high brightness and outstanding chemical stability in biological solution. The surface groups on these functionalized fluorescent dendrimers include guanidinium, mannose, and phosphatidylcholine.
Xiao, Shuzhang; Fu, Na; Peckham, Kaitlin; Smith, Bradley D.
A new strategy for the chemoselective sulfonamide N-alkylation of sulfonyl ureas under neutral and mild conditions
An efficient and chemoselective sulfonamide N-alkylation of sulfonyl ureas is described. The sulfonyl urea derivatives, prepared in situ by the addition of an amine to an arylsulfonyl isocyanate, are selectively alkylated in excellent yields under neutral and mild conditions by treatment with trialkylphosphite�dimethyl acetylenedicarboxylate at ambient temperature.
Mehdi Adib; Ehsan Sheikhi; Gita Sheikhi Moghaddam; Hamid Reza Bijanzadeh
Efficient synthesis of benzamide riboside, a potential anticancer agent.
An efficient five step synthesis of benzamide riboside (BR) amenable for a large scale synthesis has been developed. It allows for extensive pre-clinical studies of BR as a potential anticancer agent. PMID:18066762
Bonnac, Laurent F; Gao, Guang-Yao; Chen, Liqiang; Patterson, Steven E; Jayaram, Hiremagalur N; Pankiewicz, Krzysztof W
Efficient and selective synthesis of quinoline derivatives
The bromination reaction of 1,2,3,4-tetrahydroquinoline (7) was investigated by NBS and molecular bromine. One-pot synthesis is described for synthetically valuable 4,6,8-tribromoquinoline (3) and 6,8-dibromo-1,2,3,4-tetrahydroquinoline (6) on bromination of 1,2,3,4-tetrahydroquinoline (7) in efficient yields (75 and 90%, respectively). 6-Bromo- (4) and 6,8-dibromo-1,2,3,4-tetrahydroquinolines (6) were converted to 6-bromo- (1) and 6,8-dibromo quinolines (2), respectively, by aromatization with DDQ in 83 and 77%
Ayse Sahin; Osman Cakmak; Ibrahim Demirtas; Salih Okten; Ahmet Tutar
Amberlyst-15 as a Convenient Catalyst for Chemoselective Thioacetalization
A new, mild and chemoselective protection of aldehydes as 1,3-dithiolanes is described. High yields are obtained at room temperature even in the presence of ketones. Ketones may also be protected at elevated temperatures.
Robert B. Perni
Chemoselective enrichment for natural products discovery�
Natural products account for a significant proportion of modern day therapeutic agents. However, the discovery of novel compounds is hindered by the isolation process, which often relies upon extraction and chromatographic separation techniques. These methods, which are dependent upon the physicochemical properties of the compounds, have a limited ability to both purify and concentrate the minor components of a biological extract. We have devised an isolation strategy based upon an orthogonal chemical feature, namely, functional group composition. Development of a functional group-targeted method is expected to achieve exceptional resolution given the large number of distinct moieties present in natural product extracts. Here, we describe the generation of controllably reversible covalent enrichment tags for the chemoselective isolation of alcohol-containing natural products from complex mixtures.
Carlson, Erin E.
Efficient BDD Algorithms for FSM Synthesis and Verification
We describe a set of BDD based algorithms for efficient FSM synthesis and verification. We establish that the core compu- tation in both synthesis and verification is forming the image and pre-image of sets of states under the transition relatio n characterizing the design. To make these steps as efficient as possible, we address BDD variable ordering, use of parti-
Rajeev K. Ranjan; Adnan Aziz; Robert K. Brayton; Bernard Plessier; Carl Pixley
Synthesis of a selective estrogen receptor ?-modulator via asymmetric phase-transfer catalysis
An efficient asymmetric synthesis of selective estrogen receptor ?-modulator (S)-4-bromo-9a-butyl-8-chloro-6-fluoro-7-hydroxy-1,2,9,9a-tetrahydro-fluoren-3-one was developed. The route features a chemoselective aromatic chlorination reaction, an asymmetric phase-transfer-catalyzed alkylation of an indanone with efficient ee upgrade by racemate crystallization, and a robust bromination reaction using imidazole as an in situ bromine trap to avoid overreaction. The synthesis proceeds in 34% yield over 8 steps from
Mark A. Huffman; Jonathan D. Rosen; Roger N. Farr; Joseph E. Lynch
Chemoselective peptidomimetic ligation using thioacid peptides and aziridine templates.
Chemoselective peptidomimetic ligation has been made possible using thioacid peptides and NH aziridine-terminated amino acids and peptides. In the course of this reaction, a reduced amide bond is incorporated into the backbone of a peptide. This process enables incorporation of reduced cysteine, reduced substituted cysteine, reduced phenylalanine, and reduced alanine. Our method should be adaptable to other unnatural amino acid residues at the ligation site. Experiments aimed at evaluating the chemoselectivity of this process in the presence of competing thiol nucleophiles suggest high specificity at micromolar concentrations. This holds even in the presence of glutathione, which neutralizes xenobiotic electrophiles in cells. PMID:20666404
Assem, Naila; Natarajan, Aditya; Yudin, Andrei K
An efficient chemical synthesis of nicotinamide riboside (NAR) and analogues.
A simple and efficient synthesis of nicotinamide riboside (NAR) 1 and derivatives 4 and 5 via trimethylsilyl trifluoromethanesulfonate (TMSOTf)-mediated N-glycosilation followed by spontaneous deacetylation by treating with methanol is reported. PMID:11934573
Tanimori, Shinji; Ohta, Takeshi; Kirihata, Mitsunori
Chemoselective palladium-catalyzed ?-allylation of ?-boryl aldehydes.
Herein we report the development of an ?-allylation reaction of ?-boryl aldehydes that preserves the carbon-boron bond under Pd(0)/Pd(II) catalysis. A variety of ?-boryl aldehydes and allylic alcohols participate in this chemoselective transformation. The ?-allylated products were obtained as single regioisomers. PMID:22911058
St Denis, Jeffrey D; He, Zhi; Yudin, Andrei K
An efficient synthesis of loline alkaloids
Loline (1) is a small alkaloid that, in spite of its simple-looking structure, has posed surprising challenges to synthetic chemists. It has been known for more than a century and has been the subject of extensive biological investigations, but only two total syntheses have been achieved to date. Here, we report an asymmetric total synthesis of loline that, with less then ten steps, is remarkably short. Our synthesis incorporates a Sharpless epoxidation, a Grubbs olefin metathesis and an unprecedented transannular aminobromination, which converts an eight-membered cyclic carbamate into a bromopyrrolizidine. The synthesis is marked by a high degree of chemo- and stereoselectivity and gives access to several members of the loline alkaloid family. It delivers sufficient material to support a programme aimed at studying the complex interactions between plants, fungi, insects and bacteria brokered by loline alkaloids.
Cakmak, Mesut; Mayer, Peter; Trauner, Dirk
Overturning Established Chemoselectivities: Selective Reduction of Arenes over Malonates and Cyanoacetates by Photoactivated Organic Electron Donors
The prevalence of metal-based reducing reagents, including metals, metal complexes, and metal salts, has produced an empirical order of reactivity that governs our approach to chemical synthesis. However, this reactivity may be influenced by stabilization of transition states, intermediates, and products through substrate�metal bonding. This article reports that in the absence of such stabilizing interactions, established chemoselectivities can be overthrown. Thus, photoactivation of the recently developed neutral organic superelectron donor 5 selectively reduces alkyl-substituted benzene rings in the presence of activated esters and nitriles, in direct contrast to metal-based reductions, opening a new perspective on reactivity. The altered outcomes arising from the organic electron donors are attributed to selective interactions between the neutral organic donors and the arene rings of the substrates.
An efficient parallel synthesis of capsazepine and capsazepine analogs.
Capsazepine (CPZ, 1) is a well-known vanilloid receptor (VR1) antagonist that has been cited widely used in the literature. However the current synthetic methods used for the total synthesis of CPZ are lengthy, involve multiple purification steps, and produce low yields. Here we describe a new and highly efficient synthesis of benzazepine 3, a synthetic precursor of CPZ, in only two steps and 59% overall yield from a commercially available tetralone 2 via a Schmidt reaction as a key step. Moreover, we apply parallel synthesis techniques to prepare CPZ and CPZ analogs. Our approach enables the possibility of preparing larger, and more diverse libraries of CPZ analogs. PMID:15032662
Tafesse, Laykea; Kyle, Donald J
Counter ion effect in Au/Ag-catalyzed chemoselective 6-endo-dig N- and O-cyclizations of enyne-urea system: diversity-oriented synthesis of annulated indoles.
A two-step protocol for the diversity-oriented synthesis of annulated indoles following MCR-post MCR modification concept is described. The reaction initially proceeds through the annulation of 2-(2,2-dibromovinyl)aniline, an isocyanate, and a terminal alkyne in a three-component tandem format via Cu/Pd-catalyzed cross coupling to afford N-1 and C-2 functionalized indole. In the subsequent step, the enyne-urea derivative undergoes chemo- and regioselective 6-endo cyclization to afford O-cyclized product in the presence of Au(I)/AgNO3 and N-cyclized product in the presence of Au(I)/AgOTf under a post-MCR modification step. A mechanistic investigation following a recent pioneering work on the silver effect in gold catalysis (Shi, X. J. Am. Chem. Soc. 2012, 134, 9012) explains the role of counterion on Au/Ag-catalyzed regiodivergent pathways. PMID:23899005
Gupta, Sahaj; Koley, Dipankar; Ravikumar, Krishnan; Kundu, Bijoy
An efficient total synthesis of trilepisiumic acid.
Total synthesis of trilepisiumic acid (4-((3-(3,4-dihydroxyphenyl)acryloyl)oxy)-3-hydroxybenzoic acid) isolated from Trilepisium madagascariense was carried out. Doebner condensation of 3,4-dimethoxybenzaldehyde with malonic acid yielded 3,4-dimethoxycinnamic acid (2). Esterification of the latter with vanillin afforded 4-formyl-2-methoxyphenyl-3-(3,4-dimethoxy phenyl)acrylate (3) followed by permanganate oxidation in acidic medium provided the corresponding acid 4. Finally, demethylation of 4 was achieved by refluxing in hydrobromic acid to unveil the trilepisiumic acid (1). PMID:24841593
Saeed, Aamer; Qasim, Muhammad
Arylation with Unsymmetrical Diaryliodonium Salts: A Chemoselectivity Study
Phenols, anilines, and malonates have been arylated under metal-free conditions with twelve aryl(phenyl)iodonium salts in a systematic chemoselectivity study. A new �anti-ortho effect� has been identified in the arylation of malonates. Several �dummy groups� have been found that give complete chemoselectivity in the transfer of the phenyl moiety, irrespective of the nucleophile. An aryl exchange in the diaryliodonium salts has been observed under certain arylation conditions. DFT calculations have been performed to investigate the reaction mechanism and to elucidate the origins of the observed selectivities. These results are expected to facilitate the design of chiral diaryliodonium salts and the development of catalytic arylation reactions that are based on these sustainable and metal-free reagents.
Malmgren, Joel; Santoro, Stefano; Jalalian, Nazli; Himo*, Fahmi; Olofsson, Berit
Siloxyl ether functionalized resins for chemoselective enrichment of carboxylic acids.
Although the carboxylic acid moiety is prevalent in many biologically produced molecules, including natural products and proteins, methods to chemoselectively target this functional group have remained elusive. Generally, strategies that utilize carboxylate nucleophilicity also promote reactions with other nucleophiles such as amines and hydroxyls. A reagent was sought to facilitate the selective isolation of carboxylic acid containing compounds from complex mixtures. Here, the development of siloxyl ether functionalized solid supports is described. PMID:21957886
Highly efficient gold-catalyzed synthesis of dibenzocycloheptatrienes.
Dibenzocycloheptatrienes are obtained by a gold-catalyzed 7-exo-dig hydroarylation protocol in a highly efficient manner. The gold-catalyzed reaction usually gives the products in high yields and excellent selectivity. This procedure provides an easy and efficient access to dibenzocycloheptanoids, which are an interesting and unique class of natural products. This was underlined by the first total synthesis of reticuol. PMID:24771698
Pfl�sterer, Daniel; Rettenmeier, Eva; Schneider, Severin; de Las Heras Ruiz, Edgar; Rudolph, Matthias; Hashmi, A Stephen K
Efficient Synthesis of 1-Sulfonyl-1,2,3-triazoles
An efficient room temperature method for the synthesis of 1-sulfonyl-1,2,3-triazoles from in situ generated copper(I) acetylides and sulfonyl azides is described. Copper(I) thiophene-2-carboxylate (CuTC) catalyst produces the title compounds under both non-basic anhydrous and aqueous conditions in good yields.
Raushel, Jessica; Fokin, Valery V.
Wage Bargaining Versus Efficiency Wages: A Synthesis
We construct a model integrating the efficiency wage model of Shapiro�Stiglitz (1984) (SS), with an individual wage bargaining model in the Diamond�Mortensen�Pissarides (DMP) tradition where firms and workers form pairwise matches. We show that when workers may threaten to shirk on the job and there is individual wage bargaining, the wage is always higher and employment lower than in either
Jon Strand
Efficient synthesis and reactions of 1,2-dipyrrolylethynes
Various dipyrroles possess important motifs for construction of pyrrole-containing pigments. A series of 1,2-dipyrrolylethynes (4a�d) has been efficiently synthesized using an improved one-pot double Sonagashira coupling from trimethylsilylethyne and various 2-iodopyrroles. The resulting 1,2-dipyrrolylethynes were further transformed into novel indolyl-, ethenyl- and carboranyl-dipyrroles (5�7) using the Larock indole synthesis, stereoselective catalytic hydrogenation, or B10H14. Indolyl-dipyrroles were found to selectively bind fluoride ions using one pyrrolic and the indolyl NHs, whereas the carboranyl- and ethenyl-dipyrroles are potentially valuable precursors for the synthesis of porphyrin isomers and expanded pigments.
Tanui, Hillary K.; Hao, Erhong; Ihachi, Moses I.; Fronczek, Frank R.; Smith, Kevin M.; Vicente, M. Graca H.
Efficient synthesis of eudistomin U and evaluation of its cytotoxicity.
Eudistomin U is a member of a subclass of naturally occurring indole alkaloids known as ?-carbolines. These molecules are reported to have diverse biological activity and high binding affinity to DNA, which make them attractive targets for total synthesis. We describe an efficient, five-step synthesis of eudistomin U by employing two key reactions: a Bischler-Napieralski cyclization and a Suzuki cross coupling. We also describe the cytotoxicity of eudistomin U against various cancer cell lines and human pathogens, in which we observed potent antibacterial activity against Gram-positive bacteria. PMID:24930832
Roggero, Chad M; Giulietti, Jennifer M; Mulcahy, Seann P
Chemoselective small molecules that covalently modify one lysine in a non-enzyme protein in plasma
A small molecule that could bind selectively to and then react chemoselectively with a non-enzyme protein in a complex biological fluid, such as blood, could have numerous practical applications. Herein, we report a family of designed stilbenes that selectively and covalently modify the prominent plasma protein transthyretin in preference to more than 4,000 other human plasma proteins. They react chemoselectively
Sungwook Choi; Stephen Connelly; Nat�lia Reixach; Ian A. Wilson; Jeffery W. Kelly
Homogeneous and heterogeneous photoredox-catalyzed hydroxymethylation of ketones and keto esters: catalyst screening, chemoselectivity and dilution effects
Summary The homogeneous titanium- and dye-catalyzed as well as the heterogeneous semiconductor particle-catalyzed photohydroxymethylation of ketones by methanol were investigated in order to evaluate the most active photocatalyst system. Dialkoxytitanium dichlorides are the most efficient species for chemoselective hydroxymethylation of acetophenone as well as other aromatic and aliphatic ketones. Pinacol coupling is the dominant process for semiconductor catalysis and ketone reduction dominates the Ti(OiPr)4/methanol or isopropanol systems. Application of dilution effects on the TiO2 catalysis leads to an increase in hydroxymethylation at the expense of the pinacol coupling.
Reckenthaler, Melissa
Evolution of the total synthesis of (-)-okilactomycin exploiting a tandem oxy-cope rearrangement/oxidation, a Petasis-Ferrier union/rearrangement, and ring-closing metathesis.
An effective, asymmetric total synthesis of the antitumor antibiotic (-)-okilactomycin (1), as well as assignment of the absolute configuration, has been achieved exploiting a convergent strategy. Highlights of the synthesis include a diastereoselective oxy-Cope rearrangement/oxidation sequence to install the C(1) and C(13) stereogenic centers, a Petasis-Ferrier union/rearrangement to construct the highly functionalized tetrahydropyranone inscribed within the 13-membered macrocycle ring, employing for the first time a sterically demanding acetal, an intramolecular chemoselective acylation to access an embedded bicyclic lactone, and an efficient ring-closing metathesis (RCM) reaction to generate the macrocyclic ring. PMID:19170499
Smith, Amos B; Bosanac, Todd; Basu, Kallol
Evolution of the Total Synthesis of (-)-Okilactomycin Exploiting a Tandem Oxy-Cope Rearrangement/Oxidation, the Petasis-Ferrier Union/Rearrangement and Ring Closing Metathesis
An effective, asymmetric total synthesis of the antitumor antibiotic (-)-okilactomycin (1) and assignment of the absolute configuration, has been achieved exploiting a convergent strategy. Highlights of the synthesis include: a diastereoselective oxy-Cope rearrangement/oxidation sequence to install the C(1) and C(13) stereogenic centers; a Petasis-Ferrier union/rearrangement to construct the highly functionalized tetrahydropyranone inscribed within the thirteen membered macrocycle ring, employing for the first time a sterically demanding acetal; an intramolecular chemoselective acylation to access an embedded bicyclic lactone; and an efficient ring closing metathesis (RCM) reaction to generate the macrocyclic ring.
Smith, Amos B.; Bosanac, Todd; Basu, Kallol
Alginate esters via chemoselective carboxyl group modification.
Alginates are (1?4) linked linear copolysaccharides composed of ?-D-mannuronic acid (M) and its C-5 epimer, ?-L-guluronic acid (G). Several strategies for synthesis of carboxyl modified alginate derivatives exist in the literature. Most of these however employ aqueous chemistries, such as carbodiimide coupling reactions. Based on our recently discovered method for homogeneous dissolution of tetrabutylammonium (TBA)-alginate, we now describe use of tetrabutylammonium fluoride (TBAF)-based two component solvent systems as media for synthesis of carboxyl-modified alginate esters. Partially and fully esterified benzyl, butyl, ethyl, and methyl alginates were synthesized via reaction with the corresponding alkyl halides. The newly synthesized derivatives were soluble in polar aprotic solvents without the addition of TBAF. Saponification was performed to demonstrate that alkylation was completely regioselective for carboxylate groups in preference to hydroxyl groups to form esters. We demonstrate the utility of these alginate esters to enhance aqueous solubility of the flavonoid naringenin by formation of solid dispersions. PMID:24053805
Pawar, Siddhesh N; Edgar, Kevin J
Highly efficient chemoenzymatic synthesis of ?1-3-linked galactosides.
A novel D-galactosyl-?1-3-N-acetyl-D-hexosamine phosphorylase cloned from Bifidobacterium infantis (BiGalHexNAcP) was used with a recombinant E. coli K-12 galactokinase (GalK) for efficient one-pot two-enzyme synthesis of T-antigens, galacto-N-biose (Gal?1-3GalNAc), lacto-N-biose (Gal?1-3GlcNAc), and their derivatives. PMID:20830443
Yu, Hai; Thon, Vireak; Lau, Kam; Cai, Li; Chen, Yi; Mu, Shengmao; Li, Yanhong; Wang, Peng George; Chen, Xi
Synthesis of heteroglycoclusters by using orthogonal chemoselective ligations
Summary Synthetic heteroglycoclusters are being subjected to increasing interest due to their potential to serve as selective ligands for carbohydrate-binding proteins. In this paper, we describe an expedient strategy to prepare cyclopeptides displaying well-defined distributions and combinations of carbohydrates. By using both oxime ligation and copper(I)-catalyzed alkyne�azide cycloaddition, two series of compounds bearing binary combinations of ?Man, ?Fuc or ?Lac in an overall tetravalent presentation, and either 2:2 or 3:1 relative proportions, have been prepared.
Thomas, Baptiste; Fiore, Michele; Bossu, Isabelle; Dumy, Pascal
Synthesis of heteroglycoclusters by using orthogonal chemoselective ligations.
Synthetic heteroglycoclusters are being subjected to increasing interest due to their potential to serve as selective ligands for carbohydrate-binding proteins. In this paper, we describe an expedient strategy to prepare cyclopeptides displaying well-defined distributions and combinations of carbohydrates. By using both oxime ligation and copper(I)-catalyzed alkyne-azide cycloaddition, two series of compounds bearing binary combinations of ?Man, ?Fuc or ?Lac in an overall tetravalent presentation, and either 2:2 or 3:1 relative proportions, have been prepared. PMID:22509212
Thomas, Baptiste; Fiore, Michele; Bossu, Isabelle; Dumy, Pascal; Renaudet, Olivier
Regio- and chemoselective immobilization of proteins on gold surfaces.
Protein chips are powerful tools as analytical and diagnostic devices for detection of biomolecular interactions, where the proteins are covalently or noncovalently attached to biosensing surfaces to capture and detect target molecules or biomarkers. Thus, fabrication of biosensing surfaces for regio- and chemoselective immobilization of biomolecules is a crucial step for better biosensor performance. In our previous studies, a regio- and chemoselective immobilization strategy was demonstrated on glass surfaces. This strategy is now used to regioselectively attach proteins to self-assembled monolayers (SAMs) on gold surfaces. Recombinant green fluorescent protein (GFP), glutathione S-transferase (GST), and antibody-binding protein G, bearing a C-terminal CVIA motif, were prepared and a farnesyl analogue with an ?-alkyne moiety was attached to the sulfhydryl moiety in the cysteine side chain by protein farnesyltransferase. The proteins, modified with the bioorthogonal alkyne functional group, were covalently and regioselectively immobilized on thiol or dithiocarbamate (DTC) SAMs on a gold surface by a Huigsen [3 + 2] cycloaddition reaction with minimal nonspecific binding. A concentration-dependent increase of fluorescence intensity was observed in wells treated with GFP on both thiol- and DTC-SAMs. The highly ordered, densely packed layer allowed for a high loading of immobilized protein, with a concomitant increase in substrate binding capacity. The DTC-SAMs were substantially more resistant to displacement of the immobilized proteins from the gold surface by ?-mercaptoethanol than alkane-thiol SAMs. PMID:24437976
Choi, Seoung-Ryoung; Seo, Jin-Soo; Bohaty, Rochelle F H; Poulter, C Dale
Chemoselective surface immobilization of proteins through a cleavable peptide.
Surface immobilization of biomolecules is a fundamental step in several experimental techniques such as surface plasmon resonance analysis and microarrays. Oxime ligation allows reaching chemoselective protein immobilization with the retention of native-like conformation by proteins. Beside the need for chemoselective ligation of molecules to surface/particle, equally important is the controlled release of the immobilized molecules, even after a specific binding event. For this purpose, we have designed and assessed in an SPR experiment a peptide linker able to (i) anchor a given protein (enzymes, receptors, or antibodies) to a surface in a precise orientation and (ii) release the immobilized protein after selective enzymatic cleavage. These results open up the possibility to anchor to a surface a protein probe leaving bioactive sites free for interaction with substrates, ligands, antigens, or drugs and successively remove the probe-ligand complex by enzymatic cleavage. This peptide linker can be considered both an improvement of SPR analysis for macromolecular interaction and a novel strategy for drug delivery and biomaterial developments. PMID:21819154
Dettin, Monica; Muncan, Natali; Bugatti, Antonella; Grezzo, Francesca; Danesin, Roberta; Rusnati, Marco
Energy efficiency in nanoscale synthesis using nanosecond plasmas
We report a nanoscale synthesis technique using nanosecond-duration plasma discharges. Voltage pulses 12.5?kV in amplitude and 40?ns in duration were applied repetitively at 30?kHz across molybdenum electrodes in open ambient air, generating a nanosecond spark discharge that synthesized well-defined MoO3 nanoscale architectures (i.e. flakes, dots, walls, porous networks) upon polyamide and copper substrates. No nitrides were formed. The energy cost was as low as 75?eV per atom incorporated into a nanostructure, suggesting a dramatic reduction compared to other techniques using atmospheric pressure plasmas. These findings show that highly efficient synthesis at atmospheric pressure without catalysts or external substrate heating can be achieved in a simple fashion using nanosecond discharges.
Pai, David Z.; (Ken) Ostrikov, Kostya; Kumar, Shailesh; Lacoste, Deanna A.; Levchenko, Igor; Laux, Christophe O.
Energy efficiency in nanoscale synthesis using nanosecond plasmas.
We report a nanoscale synthesis technique using nanosecond-duration plasma discharges. Voltage pulses 12.5?kV in amplitude and 40?ns in duration were applied repetitively at 30?kHz across molybdenum electrodes in open ambient air, generating a nanosecond spark discharge that synthesized well-defined MoO? nanoscale architectures (i.e. flakes, dots, walls, porous networks) upon polyamide and copper substrates. No nitrides were formed. The energy cost was as low as 75?eV per atom incorporated into a nanostructure, suggesting a dramatic reduction compared to other techniques using atmospheric pressure plasmas. These findings show that highly efficient synthesis at atmospheric pressure without catalysts or external substrate heating can be achieved in a simple fashion using nanosecond discharges. PMID:23386976
Pai, David Z; Ken Ostrikov, Kostya; Kumar, Shailesh; Lacoste, Deanna A; Levchenko, Igor; Laux, Christophe O
Facile and efficient synthesis of naturally occurring carbasugars (+)-pericosines A and C.
An efficient synthesis of antitumor marine natural product (+)-pericosine A was achieved from (-)-quinic acid in 11.7% overall yield, which is 20 times better than our previously reported synthesis. The crucial steps of this synthesis include the regio- and stereoselective bromohydrination of an unstable diene and the ring opening of an epoxide. This synthetic route was applicable to a synthesis of (+)-pericosine C and also to a synthesis of (-)-pericosine C. PMID:19514797
Usami, Yoshihide; Ohsugi, Marie; Mizuki, Koji; Ichikawa, Hayato; Arimoto, Masao
Chemoselective Amination of Propargylic C(sp(3) )?H Bonds by Cobalt(II)-Based Metalloradical Catalysis.
Highly chemoselective intramolecular amination of propargylic C(sp(3) )?H bonds has been demonstrated for N-bishomopropargylic sulfamoyl azides through cobalt(II)-based metalloradical catalysis. Supported by D2h -symmetric amidoporphyrin ligand 3,5-Di(t) Bu-IbuPhyrin, the cobalt(II)-catalyzed C?H amination proceeds effectively under neutral and nonoxidative conditions without the need of any additives, and generates N2 as the only byproduct. The metalloradical amination is suitable for both secondary and tertiary propargylic C?H substrates with an unusually high degree of functional-group tolerance, thus providing a direct method for high-yielding synthesis of functionalized propargylamine derivatives. PMID:24840605
Lu, Hongjian; Li, Chaoqun; Jiang, Huiling; Lizardi, Christopher L; Zhang, X Peter
Introducing deep eutectic solvents to polar organometallic chemistry: chemoselective addition of organolithium and grignard reagents to ketones in air.
Despite their enormous synthetic relevance, the use of polar organolithium and Grignard reagents is greatly limited by their requirements of low temperatures in order to control their reactivity as well as the need of dry organic solvents and inert atmosphere protocols to avoid their fast decomposition. Breaking new ground on the applications of these commodity organometallics in synthesis under more environmentally friendly conditions, this work introduces deep eutetic solvents (DESs) as a green alternative media to carry out chemoselective additions of ketones in air at room temperature. Comparing their reactivities in DES with those observed in pure water suggest that a kinetic activation of the alkylating reagents is taking place, favoring nucleophilic addition over the competitive hydrolysis, which can be rationalized through formation of halide-rich magnesiate or lithiate species. PMID:24771680
Vidal, Cristian; Garc�a-�lvarez, Joaqu�n; Hern�n-G�mez, Alberto; Kennedy, Alan R; Hevia, Eva
Highly regioselective and chemoselective titanocene mediated Barbier-type allylation reactions.
Titanocene carboxylate 1 is an excellent chemoselective reagent for unprecedented ?-regioselective Barbier-type reactions. It constitutes the first titanocene(III) able to tolerate epoxides and readily reduced carbonyl compounds, such as aromatic and ?,?-unsaturated aldehydes. PMID:24435404
Morcillo, Sara P; Mart�nez-Perag�n, �ngela; Jakoby, Verena; Mota, Antonio J; Kube, Christian; Justicia, Jos�; Cuerva, Juan M; Gans�uer, Andreas
Thermally robust Au99(SPh)42 nanoclusters for chemoselective hydrogenation of nitrobenzaldehyde derivatives in water.
We report the synthesis and catalytic application of thermally robust gold nanoclusters formulated as Au99(SPh)42. The formula was determined by electrospray ionization and matrix-assisted laser desorption ionization mass spectrometry in conjunction with thermogravimetric analysis. The optical spectrum of Au99(SPh)42 nanoclusters shows absorption peaks at ~920 nm (1.35 eV), 730 nm (1.70 eV), 600 nm (2.07 eV), 490 nm (2.53 eV), and 400 nm (3.1 eV) in contrast to conventional gold nanoparticles, which exhibit a plasmon resonance band at 520 nm (for spherical particles). The ceria-supported Au99(SPh)42 nanoclusters were utilized as a catalyst for chemoselective hydrogenation of nitrobenzaldehyde to nitrobenzyl alcohol in water using H2 gas as the hydrogen source. The selective hydrogenation of the aldehyde group catalyzed by nanoclusters is a surprise because conventional nanogold catalysts instead give rise to the product resulting from reduction of the nitro group. The Au99(SPh)42/CeO2 catalyst gives high catalytic activity for a range of nitrobenzaldehyde derivatives and also shows excellent recyclability due to its thermal robustness. We further tested the size-dependent catalytic performance of Au25(SPh)18 and Au36(SPh)24 nanoclusters, and on the basis of their crystal structures we propose a molecular adsorption site for nitrobenzaldehyde. The nanocluster material is expected to find wide application in catalytic reactions. PMID:24568535
Li, Gao; Zeng, Chenjie; Jin, Rongchao
Amino acid-functionalized dendrimers with heterobifunctional chemoselective peripheral groups for drug delivery applications
Dendrimers have emerged as multifunctional carriers for targeted drug delivery, gene delivery and imaging. Improving the functional versatility at the surface for carrying multiple conjugation reactions is becoming vital. Typically, generation four polyamidoamine (G4-PAMAM) dendrimers bear ~64 symmetrical end groups, often requiring different spacers to conjugate various functional groups (drugs and targeting moieties), increasing the synthetic steps. In the present study, a simple one-step synthesis to convert each symmetrical end group of G4-PAMAM dendrimers into two reactive, distinct orthogonal and chemoselective groups is described. A near-complete end-capping of the dendrimers (87�93%) with amino acids results in heterobifunctional G4-PAMAM dendrimers bearing a very high (? 110) diverse peripheral end groups (OH+NHBoc, OH+COOMe, SH+NHBoc, and COOH+NHBoc). Postfunctionalization ability of these dendrimers was evaluated. The heterbifunctional groups at the dendrimer periphery could be chemoselectively conjugated to multiple moieties such as drugs (indomethacin and dexamethasone) and drugs and imaging agents (dexamethasone and FITC). These conjugations could be achieved in immediate succession without functional group conversions, eliminating the additional elaborate synthetic steps traditionally required to append specific linkers. Furthermore, one of the two functional handles at periphery was used to develop in situ forming hydrogels, whereas the other handle could be used for conjugating the drugs (e.g., dexamethasone). The heterobifunctional dendrimers with either �NH2 or SH (thiopyridyl protected form)� terminations showed in situ hydrogel formation by cross-linking with N-hydroxysuccinimide or thiol-terminated multiarm polyethylene glycol (20 kDa). The choice of amino acids as versatile linkers would enable biocompatible dendrimer scaffolds for use in drug delivery. ?-potential measurements showed drastic lowering of the charge on G4-PAMAM-NH2 dendrimers by end-capping with amino acids, whereas in the case of neutral G4-PAMAM-OH dendrimers, the charge did not increase or decrease substantially. The in vitro cytotoxicity and hemolysis assay showed that the heterobifunctional dendrimers were noncytoxic in the 100 ng/mL to 1 mg/mL concentration range. With this study, we demonstrate the development of biocompatible dendrimers bearing multiple orthogonal surface groups, enabling the attachment of drugs, imaging agents, and gel formation using minimal synthetic steps.
Navath, RS; Menjoge, AR; Wang, B; Romero, R; Kannan, S; Kannan, RM
Efficient synthesis of polysubstituted olefins using stable palladium nanocatalyst: applications in synthesis of tamoxifen and isocombretastatin a4.
A phosphine-free stable palladium nanocatalyst was used for an efficient synthesis of polysubstituted olefins from N-tosylhydrazones and aryl iodides. This methodology was successfully utilized in the synthesis of biologically important tamoxifen and isocombretastatin A4. The nanocatalyst was easily recovered and reused without any apparent loss in size and catalytic activity. PMID:25036297
Ganapathy, Dhandapani; Sekar, Govindasamy
FeCl3-catalyzed synthesis of functionally diverse dibenzo[b,f]oxepines and benzo[b]oxepines via alkyne-aldehyde metathesis.
An efficient synthesis of dibenzo[b,f]oxepines and benzo[b]oxepines via FeCl3-catalyzed alkyne-aldehyde metathesis reaction is described. Structurally diverse dibenzo[b,f]oxepines and benzo[b]oxepines have been achieved in good yields with high regio- and chemoselectivity under mild conditions. Notably, among the various catalysts such as Fe(III), Au(III), In(III), Zn(II), Ag(I) and triflic acid, the alkyne-aldehyde metathesis reaction of 2-(2'-phenylethynyl-phenyloxy)-benzaldehyde is only catalyzed by environmentally friendly and sustainable iron(III) chloride. PMID:24220112
Bera, Krishnendu; Jalal, Swapnadeep; Sarkar, Soumen; Jana, Umasish
Effect of the alpha-methyl substituent on chemoselectivity in esterase-catalyzed hydrolysis of S-acetyl sulfanylalkanoates.
The isomeric compounds 1 and 3, which differ only in the position of a methyl substituent, give opposite chemoselectivities in an esterase-catalyzed hydrolysis reaction. The esterase was chemoselective for the oxoester in 1, but for the thiol ester group in 3. A high enantioselectivity was observed for both 1 and 3. PMID:10905865
Kumar, I; Jolly, R S
Phosphinite-iminopyridine iron catalysts for chemoselective alkene hydrosilylation.
A series of new pincer iron complexes with electron-donating phosphinite-iminopyridine (PNN) ligands has been prepared and characterized. These iron compounds are efficient and selective catalysts for the anti-Markovnikov alkene hydrosilylation of primary, secondary, and tertiary silanes. More importantly, the system exhibits unprecedented functional group tolerance with reactive groups such as ketones, esters, and amides. Furthermore, the iron-catalyzed alkene hydrosilylation was successfully applied to the synthesis of a valuable insecticide, silafluofen. The electronic properties and structures of the iron complexes have been studied by spectroscopies and computational methods. Overall, the iron catalysts may provide a low-cost and environmentally benign alternative to currently employed precious metal systems for alkene hydrosilylation. PMID:24304467
Peng, Dongjie; Zhang, Yanlu; Du, Xiaoyong; Zhang, Lei; Leng, Xuebing; Walter, Marc D; Huang, Zheng
Influence of processing parameters on nanomaterials synthesis efficiency by a carbothermal reduction process
In this work, the influence of synthesis parameters on the synthesis efficiency of tin oxide nanomaterials was studied by\\u000a using the carbothermal reduction method in a sealed tube furnace. The parameters were the starting material, temperature and\\u000a time of synthesis as well as the gas flux. The starting material was tin dioxide mixed with carbon black in a molar proportion
Pedro Henrique Suman; Marcelo Ornaghi Orlandi
Highly chemoselective direct crossed aliphatic-aromatic acyloin condensations with triazolium-derived carbene catalysts.
It has been shown for the first time that triazolium precatalysts promote (in the presence of base) highly chemoselective crossed acyloin condensation reactions between aliphatic and ortho-substituted aromatic aldehydes. An o-bromine atom can serve as a temporary directing group to ensure high chemoselectivity (regardless of the nature of the other substituents on the aromatic ring) which then can be conveniently removed. The process is of broad scope and is operationally simple as it does not require the preactivation of any of the coupling partners to ensure selectivity. Preliminary data indicate that highly enantioselective variants of the reaction are feasible using chiral precatalysts. PMID:20977280
O'Toole, Sarah E; Rose, Christopher A; Gundala, Sivaji; Zeitler, Kirsten; Connon, Stephen J
Stereocontrolled access to orthogonally protected anti,anti-4-aminopiperidine-3,5-diols through chemoselective reduction of enantiopure beta-lactam cyanohydrins.
The cyanosilylation of enantiopure 4-oxoazetidine-2-carbaldehydes with tert-butyldimethylsilyl cyanide was promoted by either molecular sieves or catalytic amount of sodium carbonate to give O-silylated beta-lactam cyanohydrins with good yield and diastereoselectivity. In contrast, Lewis acids did not effectively promote the cyanosilylation under different experimental conditions, and instead hydrocyanation took place affording the corresponding free cyanohydrins in variable yield and selectivity. Starting from beta-lactam cyanohydrin hybrids, two concise, complementary stereocontrolled routes to optically pure orthogonally protected anti,anti-4-amino-3,5-piperidine diols were achieved. Key features of the first approach include chemoselective reductive opening of the beta-lactam ring with LiBH4 to a 3-amino-5-hydroxy pentanenitrile followed by reductive cyclization of a conveniently functionalized cyanomesylate derivative with NaBH4/NiCl2. The second approach involves LiAlH4 reduction of protected anti,anti-4-amino-3,5-dihydroxypiperidin-2-ones, which were easily obtained by chemoselective reduction of the cyano group in the beta-lactam cyanohydrin hybrids with NaBH4/NiCl2 and subsequent intramolecular rearrangement of the resulting amino beta-lactams. Both routes make use of an oxidative N-dearylation with diacetoxyiodobenzene of a 4-methoxyphenylamino group as a common synthetic step. Specifically, the utility of this novel reaction sequence has been demonstrated by the synthesis of fully orthogonally protected sialidase inhibitors. PMID:17867703
Alcaide, Benito; Almendros, Pedro; Cabrero, Gema; Ruiz, M Pilar
Protecting group free synthesis of urea-linked glycoconjugates: efficient synthesis of ?-urea glycosides in aqueous solution.
A method for the protecting group free synthesis of ?-urea-linked glycoconjugates has been developed. The one step process, involving reactions between urea and d-glucose, N-acetyl-d-glucosamine or d-xylose in acidic aqueous solution, furnishes the corresponding ?-urea glycosides in modest yields. This simple and efficient procedure is applicable to the synthesis of ?-urea tethered amino acid-carbohydrate conjugates. PMID:24796538
Ichikawa, Yoshiyasu; Minami, Takahiro; Kusaba, Shohei; Saeki, Nobuyoshi; Tonegawa, Yuta; Tomita, Yumiko; Nakano, Keiji; Kotsuki, Hiyoshizo; Masuda, Toshiya
Novel and Efficient One-Pot Synthesis of (Aminophenyl)carbamic Acid Esters
A novel and efficient protocol is developed for the synthesis of various (aminophenyl)carbamic acid esters from the reduction and condensation of nitrophenyl isocyanate derivatives. The reaction takes place in various hydroxy derivatives such as alcohols or phenols under a hydrogen atmosphere using Raney nickel as catalyst. Products are obtained by a convenient one�pot synthesis with excellent yields and short reaction
Antonio Garofalo; Laurence Goossens; Perrine Six; Nicolas Lebegue; Patrick Depreux
Effects of Speech Synthesis on the Proofreading Efficiency of Postsecondary Students with Learning Disabilities.
This study investigated effects of speech synthesis on proofreading efficiency among 33 postsecondary students with learning disabilities. Using a speech synthesis system enabled subjects to detect a significantly higher percentage of errors, though having text read aloud by another person remained the most effective way to find�
Raskind, Marshall H.; Higgins, Eleanor
Efficient NES-dependent protein nuclear export requires ongoing synthesis and export of mRNAs
The mechanisms regulating nuclear export of proteins are not fully understood. To investigate whether the efficiency of protein nuclear export may depend on ongoing RNA synthesis and\\/or mRNA nuclear export, we used a microinjection approach with a fluorescent reporter protein containing a nuclear export signal (NES) and scored protein export in human fibroblasts under conditions when the synthesis or export
Heather M. O'Hagan; Mats Ljungman
MAELSTROM: efficient simulation-based synthesis for custom analog cells
Analog synthesis tools have failed to migrate into mainstream use primarily because of difficulties in reconciling the simplified models required for synthesis with the industrial-strength simulation environments required for validation. M AELSTROM is a new approach that synthesizes a circuit using the same simulation environment created to validate the circuit. We introduce a novel genetic\\/ annealing optimizer, and leverage network
Michael Krasnicki; Rodney Phelps; Rob A. Rutenbar; L. Richard Carley
An efficient synthesis of 3-amino-2-arylimidazo[1,2- a]pyridines
An efficient synthesis of 3-amino-2-arylimidazo[1,2-a]pyridines is described via a novel multicomponent reaction between 2-aminopyridines, benzaldehydes and imidazoline-2,4,5-trione under solvent-free conditions.
Mehdi Adib; Esmail Sheibani; Long-Guan Zhu; Peiman Mirzaei
Efficient synthesis of tetrasubstituted thiophenes by reaction of benzoyl isothiocyanates, ethyl bromopyruvate and enaminones
An efficient synthesis of ethyl 2-(4-acetyl-5-benzoylamino-3-methyl-2-thienyl)-2-oxoacetates is described via reaction between benzoyl isothiocyanates and ethyl bromopyruvate in the presence of enaminones.
Issa Yavari; Zinatossadat Hossaini; Maryam Sabbaghan
Formation of glucoraphanin by chemoselective oxidation of natural glucoerucin: A chemoenzymatic route to sulforaphane
A new semi-synthetic way to produce glucoraphanin (2), the bio-precursor of the potential anticarcinogen sulforaphane (3), has been developed. Starting from glucoerucin (1), isolated from ripe seeds of Eruca sativa, glucoraphanin was obtained through chemoselective oxidation. Controlled myrosinase-catalysed hydrolysis of this precursor quantitatively afforded sulforaphane.
R. Iori; R. Bernardi; D. Gueyrard; P. Rollin; S. Palmieri
Chemoselective nanoporous membranes via chemically directed assembly of nanoparticles and dendrimers.
Chemoselective nanoporous membranes: tunably porous membranes with embedded functionalities are generated using a template-free, chemically directed nanoparticle-dendrimer (NP-Den) network assembly. This approach provides a direction in the design of post-functionalizable nanoporous membranes for distinguishing both organic molecules and proteins with excellent chemo- and bioselectivity. PMID:22915042
Park, Myoung-Hwan; Subramani, Chandramouleeswaran; Rana, Subinoy; Rotello, Vincent M
Site-specific cellular delivery of quantum dots with chemoselectively-assembled modular peptides.
Modular peptides displaying both quantum dot bioconjugation motifs and specific subcellular targeting domains were constructed using a chemoselective aniline-catalyzed hydrazone coupling chemistry. Peptides were ratiometrically assembled onto quantum dots to facilitate their specific delivery to either the plasma membrane, endosomes, the cytosol or the mitochondria of target cells. PMID:23759873
Delehanty, James B; Blanco-Canosa, Juan B; Bradburne, Christopher E; Susumu, Kimihiro; Stewart, Michael H; Prasuhn, Duane E; Dawson, Philip E; Medintz, Igor L
Highly regio- and chemoselective palladium-catalyzed propargylallylation of activated olefins: a novel route to 1,7-enyne derivatives.
An efficient method for the synthesis of 1,7-enyne derivatives via phosphine-palladium-catalyzed three-component assembling of activated olefins, allylic chlorides, and allenylstannanes is described. Substituted arylethylidene malononitriles 1a-g (RCH=C(CN)(2): R = C(6)H(5) (1a), p-ClC(6)H(4) (1b), p-OMeC(6)H(4) (1c), p-NO(2)C(6)H(4) (1d), 1-naphthyl (1e), 2-furyl (1f), and 2-thienyl (1g)) undergo propargylallylation with allylic chlorides 2a-e (allyl chloride (2a), methallyl chloride (2b), 4-chloropent-2-ene (2c), cinnamyl chloride (2d), and 3-chlorocyclohexene (2e)) and n-tributylallenylstannane (n-Bu(3)SnCH=C=CH(2), 3a) in the presence of Pd(PPh(3))(4) in toluene to afford the corresponding 1,7-enyne derivatives 4a-m in good to excellent yields. The catalytic reaction is highly regioselective, with the propargyl group adding to the carbon where the R group is attached and the allyl group adding to the carbon connected to the CN groups of activated olefins 1a-g. The present catalytic reaction is successfully extended to substituted arylethylidene-1,3-indanediones 5a-j (RCH = (1,3-indanedione): R = C(6)H(5) (5a), p-ClC(6)H(4) (5b), p-BrC(6)H(4) (5c), p-OMeC(6)H(4) (5d), p-NO(2)C(6)H(4) (5e), p-CNC(6)H(4) (5f), p-biphenyl (5g), 1-naphthyl (5h), 2-thienyl (5i), and 2-benzo[b]furane-2-yl (5j)) and substituted 2,2-dimethyl-5-(arylethylidene)-1,3-dioxane-4,6-diones 7a,b (RCH = (1,3-dioxane-4,6-dione): R = p-NO(2)C(6)H(4) (7a), p-OMeC(6)H(4) (7b)). The three-component assembling of these substrates with allylic chlorides (2a,b,d,e) and n-tributylallenylstannane (n-Bu(3)SnCH=C=CH(2), 3a) proceeds smoothly to afford the corresponding 1,7-enyne derivatives 6a-m and 8a-d in good to excellent yields. The catalytic propargylallylation can be further applied to the activated dienes, C(6)H(5)CH=CH=CR(2) (R(2) = (CN)(2) (9a), 1,3-indanedione (9b), 2,2-dimethyl-1,3-dioxane-4,6-dione (9c)), with allylic chlorides (2a,b,d) and allenylstannane 3a to give regio- and chemoselective 1,2-addition products 10a-h in good to excellent yields. A plausible mechanism based on an eta(1)-allenyl eta(3)-allyl palladium intermediate is proposed to account for the catalytic three-component reaction. PMID:15176830
Jeganmohan, Masilamani; Shanmugasundaram, Muthian; Cheng, Chien-Hong
Substrate-directable electron transfer reactions. Dramatic rate enhancement in the chemoselective reduction of cyclic esters using SmI2-H2O: mechanism, scope, and synthetic utility.
Substrate-directable reactions play a pivotal role in organic synthesis, but are uncommon in reactions proceeding via radical mechanisms. Herein, we provide experimental evidence showing dramatic rate acceleration in the Sm(II)-mediated reduction of cyclic esters that is enabled by transient chelation between a directing group and the lanthanide center. This process allows unprecedented chemoselectivity in the reduction of cyclic esters using SmI2-H2O and for the first time proceeds with a broad substrate scope. Initial studies on the origin of selectivity and synthetic application to form carbon-carbon bonds are also disclosed. PMID:24079360
Szostak, Michal; Spain, Malcolm; Choquette, Kimberly A; Flowers, Robert A; Procter, David J
Chemoselectivity in oxidative coupling of bifunctional nucleophiles with dinucleoside H-phosphonate and dinucleoside H-phosphonothioate diesters.
Chemoselectivity and stereospecificity of iodine mediated oxidative couplings using separate diastereomers of dinucleoside H-phosphonate and H-phosphonothioate with various N- and O-binucleophiles were investigated. PMID:14565444
Nilsson, Johan; Kraszewski, Adam; Stawinski, Jacek
Efficient new-view synthesis using pairwise dictionary priors
New-view synthesis (NVS) using texture priors (as op- posed to surface-smoothness priors) can yield high quality results, but the standard formulation is in terms of large- clique Markov Random Fields (MRFs). Only local opti- mization methods such as iterated conditional modes, which are prone to fall into local minima close to the initial esti- mate, are practical for solving these
Oliver J. Woodford; Ian D. Reid; Andrew W. Fitzgibbon
Efficient ytterbium triflate catalyzed microwave-assisted synthesis of 3-acylacrylic acid building blocks.
The derivatives of 4-(hetero)aryl-4-oxobut-2-enoic acid are useful as building blocks in the synthesis of biologically active compounds. An efficient general protocol for the synthesis of these building blocks was developed. This method combines microwave assistance and ytterbium triflate catalyst and allows the fast preparation of the target acids starting from different (hetero)aromatic ketones and glyoxylic acid monohydrate giving pure products in 52-75% isolated yields. PMID:18715040
Tolstoluzhsky, Nikita V; Gorobets, Nikolay Yu; Kolos, Nadezhda N; Desenko, Sergey M
Semi-vectorization: an efficient technique for synthesis and analysis of gravity gradiometry data
The harmonic synthesis and analysis of the elements of gravitational tensor can be done in few minutes if a suitable programming\\u000a algorithm is used. Vectorization is an efficient technique for such processes, but the size of matrices will increase when\\u000a the resolution of synthesis or analysis is high; say higher than 0.5�?�?0.5�. Here, we present a technique to manage the
Mehdi Eshagh; Makan Abdollahzadeh
Efficient Solid-Phase Synthesis of pppRNA by Using Product-Specific Labeling.
A novel solid-phase synthesis and purification strategy for 5'-triphosphate oligonucleotides by using lipophilic tagging of the triphosphate moiety is reported. This is based on triphosphate synthesis with 5'-O-cyclotriphosphate intermediates, whereby a lipophilic tag, such as decylamine, is introduced during the ring-opening reaction to give a linear gamma-phosphate-tagged species. This method enables the highly efficient synthesis of 5'-triphosphorylated RNA derivatives and their gamma-phosphate-substituted analogues and will especially facilitate the advancement of therapeutic approaches that make use of 5'-triphosphate oligonucleotides as potent activators of the cytosolic immune sensor RIG-I. PMID:24668741
Goldeck, M; Tuschl, T; Hartmann, G; Ludwig, J
Efficient synthesis of fluorothiosparfosic acid analogues with potential antitumoral activity.
In this paper, we describe a short synthesis of N-(phosphonoacetyl)-L-aspartate (PALA) analogues. The mono- and difluorinated thioacetamide precursors were prepared in one step from methyl (diethoxyphosphono)di- and monofluoromethyldithioacetates 8 and 11 as starting materials. Antiproliferating properties on a L1210 strain and ATCase inhibition of these new compounds are disclosed. ThioPALA(FF) 5c showed a remarkable cytotoxic activity towards murine leukemia L1210, when used as tetraester. PMID:15975800
Pfund, Emmanuel; Lequeux, Thierry; Masson, Serge; Vazeux, Michel; Cordi, Alex; Pierre, Alain; Serre, Val�rie; Herv�, Guy
Chemoselective attachment of small molecule effector functionality to human adenoviruses facilitates gene delivery to cancer cells
Azide-enabled adenovirus for gene delivery: We demonstrate here a novel two-step �click� labeling process in which adenoviral particles are first metabolically labeled during production with unnatural azido sugars. Subsequent chemoselective modification allows access to viruses decorated with a broad array of effector functionality. Adenoviruses modified with folate, a known cancer-targeting motif, demonstrated a marked increase in gene delivery to a murine cancer cell line.
Banerjee, Partha Sarathi; Ostapachuk, Philomena; Hearing, Patrick
Efficiency, error and yield in light-directed maskless synthesis of DNA microarrays
Background Light-directed in situ synthesis of DNA microarrays using computer-controlled projection from a digital micromirror device--maskless array synthesis (MAS)--has proved to be successful at both commercial and laboratory scales. The chemical synthetic cycle in MAS is quite similar to that of conventional solid-phase synthesis of oligonucleotides, but the complexity of microarrays and unique synthesis kinetics on the glass substrate require a careful tuning of parameters and unique modifications to the synthesis cycle to obtain optimal deprotection and phosphoramidite coupling. In addition, unintended deprotection due to scattering and diffraction introduce insertion errors that contribute significantly to the overall error rate. Results Stepwise phosphoramidite coupling yields have been greatly improved and are now comparable to those obtained in solid phase synthesis of oligonucleotides. Extended chemical exposure in the synthesis of complex, long oligonucleotide arrays result in lower--but still high--final average yields which approach 99%. The new synthesis chemistry includes elimination of the standard oxidation until the final step, and improved coupling and light deprotection. Coupling Insertions due to stray light are the limiting factor in sequence quality for oligonucleotide synthesis for gene assembly. Diffraction and local flare are by far the largest contributors to loss of optical contrast. Conclusions Maskless array synthesis is an efficient and versatile method for synthesizing high density arrays of long oligonucleotides for hybridization- and other molecular binding-based experiments. For applications requiring high sequence purity, such as gene assembly, diffraction and flare remain significant obstacles, but can be significantly reduced with straightforward experimental strategies.
Rolling Circle DNA Synthesis: Small Circular Oligonucleotides as Efficient Templates for DNA Polymerases
We report that small, single-stranded circular DNA oligonucleotides 26 to 74 nucleotides (nt) in size can behave as catalytic templates for DNA synthesis by several DNA polymerase enzymes. The DNA products are repeating end-to-end multimeric copies of the synthetic circular DNAs, and range from 1 000 to > 12 000 nucleotides in length. Several aspects of this reaction are unusual: first, the synthesis proceeds efficiently despite the curvature and small size of the circles, some of which have diameters significantly smaller than that of the enzyme itself. Second, the synthesis can proceed hundreds of times around the circle, while rolling replication of larger circular plasmid DNAs requires other proteins for processive synthesis. Finally, the synthesis scheme produces multiple copies of the template without the requirement for either heating or cooling cycles and requires less than stoichiometric amounts of primer, unlike other DNA synthesis methods. We report on the scope of this reaction, and demonstrate that the multimeric products can be cleaved enzymatically to short, sequence-defined oligodeoxynucleotides. This new approach to DNA synthesis may be a practical way to produce useful repeating DNAs, and combined with DNA cleavage strategies, it may represent a useful enzymatic approach to short, sequence-defined oligodeoxynucleotides.
Liu, Dongyu; Daubendiek, Sarah L.; Zillman, Martin A.; Ryan, Kevin
Mild and efficient desymmetrization of diynes via hydroamination: application to the synthesis of (+/-)-monomorine I.
An efficient silver-catalyzed desymmetrization of amino diynes via hydroamination is reported. A variety of functionalized 1-pyrroline derivatives were synthesized in 73% to 88% isolated yields (>98% by (1)H NMR in some cases). The usefulness of this mild hydroamination method was further shown by the desymmetrization of unprotected tert-hydroxy diynes. Structures of two transition states have been studied computationally. An application of this method was demonstrated by a short and efficient synthesis of (+/-)-monomorine I. PMID:20088529
Iska, Vijaya Bhaskara Reddy; Verdolino, Vincenzo; Wiest, Olaf; Helquist, Paul
Efficient synthesis of graphene sheets using pyrrole as a reducing agent
The efficient synthesis of graphene sheets using pyrrole as a reducing agent was explored. The obtained graphene sheets were dispersible in organic solvents such as ethanol, isopropanol, N,N-dimethylformamide, N-methylpyrrolidone, dimethylsulfoxide, tetrahydrofuran, and acetone. During this reduction reaction, pyrrole was oxidized, forming oxidation product of pyrrole and adsorbed on the graphene sheets surface by ?�? interaction. The oxidation product of pyrrole
Chellachamy Anbalagan Amarnath; Chang Eui Hong; Nam Hoon Kim; Bon-Cheol Ku; Tapas Kuila; Joong Hee Lee
Silica supported phosphomolybdic acid: an efficient heterogeneous catalyst for Friedlander synthesis of quinolines.
Silica supported phosphomolybdic acid, an eco-friendly heterogeneous catalyst, has been found to be highly efficient for Friedlander synthesis of quinolines in excellent yields. A variety of ketones afford the quinolines smoothly. The catalyst can be easily recovered and reused. PMID:18591832
Das, Biswanath; Krishnaiah, Martha; Laxminarayana, Keetha; Nandankumar, Duddukuri
Tetrabutylammonium hydrogen sulfate catalyzed eco-friendly and efficient synthesis of glycosyl 1,4-dihydropyridines
An efficient and eco-friendly synthesis of glycosyl 1,4-dihydropyridines has been achieved by a three-component reaction of ?-keto esters or ketones, enamines and glycosyl aldehydes in the presence of tetrabutylammonium hydrogen sulfate as catalyst in diethylene glycol.
Neetu Tewari; Namrata Dwivedi; Rama P. Tripathi
An efficient one-pot synthesis of polyhydroquinolines at room temperature using HY-zeolite.
An efficient one-pot synthesis of polyhydroquinolines by four-component coupling reactions of aldehydes, ethyl acetoacetate, dimedone and ammonium acetate in the presence of HY-zeolite at ambient temperature has been achieved. The conversions took shorter times to form the products in excellent yields. HY-zeolite can be recovered and reused. PMID:16819229
Das, Biswanath; Ravikanth, Bommena; Ramu, Ravirala; Vittal Rao, Bommena
A simple and efficient synthesis of 2,3-diarylnaphthofurans using sequential hydroarylation/Heck oxyarylation.
An efficient and simple strategy has been developed for the synthesis of 2,3-diarylnaphthofurans using sequential hydroarylation of naphthols and alkynes in the presence of In(OTf)3 under microwave irradiation followed by one-pot Heck-oxyarylation of generated 1-substituted-?-hydroxy styrenes. PMID:23586966
Rao, V Kameshwara; Shelke, Ganesh M; Tiwari, Rakesh; Parang, Keykavous; Kumar, Anil
Magnesium bis(monoperoxyphthalate) hexahydrate as mild and efficient oxidant for the synthesis of selenones
Summary A new, efficient and mild method for the direct oxidation of selenides to selenones using magnesium bis(monoperoxyphthalate) hexahydrate (MMPP) has been developed. Noteworthy this transformation proceeds at room temperature, employs a cheap and safety oxidant and has a broad functional group tolerance. Moreover, the produced selenones could be useful intermediates for the synthesis of different heterocyclic compounds.
Curini, Massimo; Rosati, Ornelio; Minuti, Lucio
Gold-catalyzed intermolecular C-S bond formation: efficient synthesis of ?-substituted vinyl sulfones.
A general method for the synthesis of ?-substituted vinyl sulfones makes use of a combination of a triazole gold complex and gallium triflate. This efficient C?S bond formation between simple terminal alkynes and sulfinic acids provides access to various ?-substituted vinyl sulfones. PMID:24692330
Xi, Yumeng; Dong, Boliang; McClain, Edward J; Wang, Qiaoyi; Gregg, Tesia L; Akhmedov, Novruz G; Petersen, Jeffrey L; Shi, Xiaodong
An Efficient Synthesis of Trialkyl N Alkyl6-methyl-2-pyridone-3,4,5-tricarboxylates
Summary.��An efficient synthesis of trialkyl N-alkyl-6-methyl-2-pyridone-3,4,5-tricarboxylates from three-component reaction of the zwitterions generated from dialkyl acetylenedicarboxylates\\u000a and alkyl isocyanides with alkyl 2-chloroacetoacetates is described.
Issa Yavari; Hasan Zare
An efficient synthesis of fluorinated azaheterocycles by aminocyclization of alkenes.
A general and efficient approach to important fluorinated azaheterocycles has been developed by incorporating nucleophilic fluorination into alkene difunctionalization. This intramolecular aminofluorination transformation of alkenes has been achieved via the aminocyclization of reactive unsaturated N-iodoamines, which can be generated in situ from either unsaturated N-chloramines or their amine precursors in a one-pot protocol. PMID:23544433
Huang, Hai-Tsang; Lacy, Tyler C; B?achut, Barbara; Ortiz, Gerardo X; Wang, Qiu
Facile, efficient, and diastereoselective synthesis of heterohelicene-like molecules.
A concise and efficient route to new and interesting heterohelicene-like molecules has been developed through the one-pot, cascade reductive coupling reaction of o-hydroxydiimines or o-nitrodiimines and triphosgene in the presence of TiCl4/Sm. Purification of the final products only required a single recrystallization leading to high purity. High diastereoselectivity was also achieved, and two structures of the final products were confirmed by X-ray diffraction analysis. PMID:23451838
Lin, Wei; Dou, Guo-Lan; Hu, Ming-Hua; Cao, Cheng-Pao; Huang, Zhi-Bin; Shi, Da-Qing
An efficient synthesis of (+/-)-trichostatic Acid and analogues: a new route to (+/-)-trichostatin A.
An efficient synthesis of rac-trichostatic acid (1) and its analogues is reported starting from a commercially available aldehyde. Further manipulations of rac-1 led to rac-trichostatin A (TSA). Construction of the desired molecular architecture entails a two-component union, achieved through an in situ hydroboration followed by a Suzuki-Miyaura coupling with 2. The requisite homopropargyl alcohol was synthesized by exploiting allenylindium chemistry. This new protocol paved the way for the synthesis of analogues of trichostatic acid and hence TSA. PMID:20104892
Chatterjee, Anamitra; Richer, Joshua; Hulett, Tyler; Iska, Vijaya Bhaskara Reddy; Wiest, Olaf; Helquist, Paul
Chemoselective biocatalytic reduction of conjugated nitroalkenes: new application for an Escherichia coli BL21(DE3) expression strain.
Chemoselective reduction of activated carbon-carbon double bond in conjugated nitroalkenes was achieved using Escherichia coli BL21(DE3) whole cells. Nine different substrates have been used furnishing the reduced products in moderate to good yields. 1-Nitro-4-phenyl-1,3-butadiene and (2-nitro-1-propenyl)benzene were successfully biotransformed with corresponding product yields of 54% and 45% respectively. Using this simple and environmentally friendly system 2-(2-nitropropyl)pyridine and 2-(2-nitropropyl)naphthalene were synthesized and characterized for the first time. High substrate conversion efficiency was coupled with low enantioselectivity, however 29% enantiomeric excess was detected in the case of 2-(2-nitropropyl)pyridine. It was shown that electronic properties of the aromatic ring, which affected polarity of the double bond, were not highly influential factors in the reduction process, but the presence of the nitro functionality was essential for the reaction to proceed. 1-Phenyl-4-nitro-1,3-butadiene could not be biotransformed by whole cells of Pseudomonas putida KT2440 or Bacillus subtilis 168 while it was successfully reduced by E. coli DH5? but with lower efficiency in comparison to E. coli BL21(DE3). Knockout mutant affected in nemA gene coding for N-ethylmaleimide reductase (BL21?nemA) could still catalyze bioreductions suggesting multiple active reductases within E. coli BL21(DE3) biocatalyst. The described biocatalytic reduction of substituted nitroalkenes provides an efficient route for the preparation of the corresponding nitroalkanes and introduces the new application of the strain traditionally utilized for recombinant protein expression. PMID:24835095
Jovanovic, Predrag; Jeremic, Sanja; Djokic, Lidija; Savic, Vladimir; Radivojevic, Jelena; Maslak, Veselin; Ivkovic, Branka; Vasiljevic, Branka; Nikodinovic-Runic, Jasmina
Polymer synthesis by enzymatic catalysis.
Using biocatalysts as enzymes for in vitro polymer synthesis is a relatively new (third) stream that has become popular in the past two decades, following a first stream using catalysts of acids, bases, radical species, and so on, used since 1920s, and a second stream using catalysts of transition metals and rare metals since 1950s. Enzymatic catalysis is environmentally benign, yet allows the synthesis of various natural and unnatural polymers that have well-defined structures with controlled stereochemistry, regioselectivity, and chemoselectivity. This review will focus on recent developments in enzyme-catalyzed polymer synthesis in the areas of polysaccharides, polyesters, and polyaromatics, as well as polymer modification. PMID:20022287
Kadokawa, Jun-ichi; Kobayashi, Shiro
Highly Efficient Synthesis of Clean Biofuels from Biomass Using FeCuZnAlK Catalyst
Highly efficient synthesis of clean biofuels using the bio-syngas obtained from biomass gasification was performed over Fe1.5Cu1Zn1Al1K0.117 catalyst. The maximum biofuel yield from the bio-syngas reaches about 1.59 kg biofuels/(kgcatal�h) with a contribution of 0.57 kg alcohols/(kgcatal�h) and 1.02 kg liquid hydrocarbons/(kgcatal�h). The alcohol products in the resulting biofuels were dominated by the C2+ alcohols (mainly C2�C6 alcohols) with a content of 73.55%-89.98%. The selectivity of the liquid hydrocarbons (C5+) in the hydrocarbon products ranges from 60.37% to 70.94%. The synthesis biofuels also possess a higher heat value of 40.53-41.49 MJ/kg. The effects of the synthesis conditions, including temperature, pressure, and gas hourly space velocity, on the biofuel synthesis were investigated in detail. The catalyst features were characterized by inductively coupled plasma and atomic emission spectroscopy, X-ray diffraction, temperature programmed reduction, and the N2 adsorption-desorption isotherms measurements. The present biofuel synthesis with a higher biofuel yield and a higher selectivity of liquid hydrocarbons and C2+ alcohols may be a potentially useful route to produce clean biofuels and chemicals from biomass.
Qiu, Song-bai; Xu, Yong; Ye, Tong-qi; Gong, Fei-yan; Yang, Zhi; Yamamoto, Mitsuo; Liu, Yong; Li, Quan-xin
Information and Efficiency in the Nervous System--A Synthesis
In systems biology, questions concerning the molecular and cellular makeup of an organism are of utmost importance, especially when trying to understand how unreliable components�like genetic circuits, biochemical cascades, and ion channels, among others�enable reliable and adaptive behaviour. The repertoire and speed of biological computations are limited by thermodynamic or metabolic constraints: an example can be found in neurons, where fluctuations in biophysical states limit the information they can encode�with almost 20�60% of the total energy allocated for the brain used for signalling purposes, either via action potentials or by synaptic transmission. Here, we consider the imperatives for neurons to optimise computational and metabolic efficiency, wherein benefits and costs trade-off against each other in the context of self-organised and adaptive behaviour. In particular, we try to link information theoretic (variational) and thermodynamic (Helmholtz) free-energy formulations of neuronal processing and show how they are related in a fundamental way through a complexity minimisation lemma.
Sengupta, Biswa; Stemmler, Martin B.; Friston, Karl J.
Chemoselective reduction and self-immolation based FRET probes for detecting hydrogen sulfide in solution and in cells.
Hydrogen sulfide (H2S) has been regarded as the third gaseous transmitter. Based on the mechanism of chemoselective azido reduction and self-immolation, five fluorescence resonance energy transfer (FRET) probes for the detection of H2S were designed and synthesized. The effect of functional substitution of the self-immolative moiety on azido reduction and quinone-methide rearrangement were investigated. Their fluorescence responses and chemoselectivity for H2S detection were evaluated in solutions and in cells. This strategy may provide a general route for designing H2S probes with many commercially available FRET pairs. PMID:24962216
Chen, Bifeng; Wang, Peng; Jin, Qingqing; Tang, Xinjing
Highly chemoselective methylation and esterification reactions with dimethyl carbonate in the presence of NaY faujasite. The case of mercaptophenols, mercaptobenzoic acids, and carboxylic acids bearing OH substituents.
In the presence of NaY faujasite, the reactions of dimethyl carbonate (DMC) with several ambident nucleophiles such as o- and p-mercaptophenols (1a,b), o- and p-mercaptobenzoic acids (2a,b), o- and p-hydroxybenzoic acids (3a,b), mandelic and phenyllactic acids (4, 5), have been explored under batch conditions. Highly chemoselective reactions can be performed: at 150 degrees C, compounds 1 and 2 undergo only a S-methylation reaction, without affecting OH and CO2H groups; at 165 degrees C, acids 3-5 form the corresponding methyl esters, while both their aromatic and aliphatic OH substituents are fully preserved from methylation and/or transesterification processes. Typical selectivities are of 90-98% and isolated yields of products (S-methyl derivatives and methyl esters, respectively) are in the range of 85-96%. A comparative study with K2CO3 as a catalyst is also reported. Although the base (K2CO3) turns out to be more active than the zeolite, the chemoselectivity is elusive: compounds 2a,b undergo simultaneous S-methylation and esterification reactions, and acids 3-5 yield complex mixtures of products of O-methylation, O-methoxycarbonylation, and esterification of their OH and CO2H groups, respectively. Overall, the combined use of a nontoxic reagent/solvent (DMC) and a safe promoter (NaY) imparts a genuine ecofriendly nature to the investigated synthesis. PMID:16468795
Selva, Maurizio; Tundo, Pietro
Use of Bacillus brevis for Efficient Synthesis and Secretion of Human Epidermal Growth Factor
Using previously isolated Bacillus brevis strains that secrete large amounts of proteins but little protease into the medium, we have developed a host-vector system for very efficient synthesis and secretion of heterologous proteins. The multiple promoters and the signal-peptide-coding region of the MWP gene, a structural gene for one of the major cell wall proteins of B. brevis strain 47,
Hideo Yamagata; Kazuo Nakahama; Yutaka Suzuki; Atsushi Kakinuma; Norihiro Tsukagoshi; Shigezo Udaka
An exceptionally simple and efficient synthesis of 6-methyl-6-vinylfulvene, and its oxidative transformations
A new efficient synthesis of 6-methyl-6-vinylfulvene was developed, starting from the 6-(2-hydroxyethyl)-6-methylfulvene. With larger quantities of the title compound in hand, its photooxygenation with singlet oxygen was studied. Cyclization of the cyclopropanone intermediate to both vinyl moieties in the unsaturated system was observed, whereas the saturated endoperoxide gave mostly the cyclopentenone derivative. m-CPBA attacks exclusively the endocyclic double bonds and gives the 3-cyclopentenones via the unstable epoxides.
Erden, Ihsan; Gartner, Christian
Simple, efficient in vitro synthesis of capped RNA useful for direct expression of cloned eukaryotic genes.
A simple and efficient method for direct in vitro synthesis of capped transcripts of cloned eukaryotic genes is described. As an example capped transcripts were made from a plasmid containing the human fibroblast interferon gene cloned under the control of a prokaryotic promoter. These transcripts were translated in vivo in Xenopus laevis oocytes and in vitro in reticulocyte and in wheat germ cell-free protein synthesizing systems. Images
Contreras, R; Cheroutre, H; Degrave, W; Fiers, W
Efficient Block Diagram Synthesis of DSP Kernels for the TMS320C6701
In this paper, an overview of rapid prototyping system using MATLAB RTW and TMS320C6701-EVM is presented. The MATLAB RTW generated ANSI C -code from block diagram has very poor real-time implementation benchmarks for DSP kernels. To improve the performance, we have developed an efficient method for direct synthesis of block diagram programming using optimised C-assembly DSP code for real-time signal
K H Hong; W S Gan; Y K Chong; S E Tan
Au(I)-catalyzed efficient synthesis of functionalized bicyclo[3.2.0]heptanes.
An efficient Au(I)-catalyzed synthesis of highly strained and functionalized bicyclo[3.2.0]heptanes is developed. Subsequent couplings with various nucleophiles offer additional structural features/complexity. These one-pot, three-component reactions are proposed to proceed via a key 1,3-dipolar cycloaddition between a Au carbenoid-containing carbonyl ylide and ethyl vinyl ether. PMID:18465856
Li, Guotao; Huang, Xiaogen; Zhang, Liming
Copper Perchlorate Hexahydrate: An Efficient Catalyst for the Green Synthesis of Polyhydroquinolines under Ultrasonication
Copper perchlorate hexahydrate as an efficient catalyst was used for the synthesis of polyhydroquinolines by four-component condensation reaction of aldehyde, ethyl acetoacetate, dimedone, and ammonium acetate in excellent yields and short reaction times at room temperature under ultrasound irradiation. This novel synthetic method is especially favoured because it provides a synergy between copper perchlorate hexahydrate and ultrasound irradiation which offers the advantages of high yields, short reaction times, simplicity, and easy workup compared to the conventional methods reported in the literature.
Puri, Saurabh; Kaur, Balbir; Parmar, Anupama; Kumar, Harish
Temporary Restraints to Overcome Steric Obstacles--Efficient Strategy for the Synthesis of Mycalamide B**
Restrain and Release: An efficient synthesis of mycalamide B is reported. The synthetic route features (a) a one-pot Mukaiyama�Michael/epoxidation sequence to introduce three of the stereocenters found in the natural product, (b) an intramolecular isocyanate trapping to produce a rigid 10-membered cyclic carbamate, and (c) the selective opening of the cyclic carbamate to reveal the fully constructed natural product.
Jewett, John C.; Rawal, Viresh H.
Diels-alder reactions of styrylcyclohexenones: an efficient procedure for the synthesis of substituted dehydrodecaline derivatives.
The Diels-Alder reaction of styrylcyclohex-2-enone derivatives 1 with N-phenylmaleimide was shown to be an efficient pathway for the synthesis of substituted dehydrodecaline derivatives. At elevated temperatures, mixtures of endo/exo adducts were formed, while in the presence of TiCl4 exclusive formation of the endo stereoisomer was observed. Spectroscopic analysis and X-ray crystallography confirmed the formation of the endo adducts. PMID:24062124
Abaee, M Saeed; Mojtahedi, Mohammad M; Rezaei, M Taghi; Khavasi, Hamid Reza
Efficient, Ecofriendly, and Practical Process for the Synthesis of Quinoxalines Catalyzed by Amberlyst-15 in Aqueous Media
Amberlyst-15\\/H2O has been used as an efficient and environmentally friendly catalytic system for the synthesis of quinoxalines. The present methodology offers several advantages, such as excellent yields, short reaction time, and simple workup.
Ju-Yan Liu; Jing Liu; Jia-Di Wang; De-Quan Jiao; Hai-Wang Liu
Eco-friendly polyethylene glycol-400: a rapid and efficient recyclable reaction medium for the synthesis of thiazole derivatives
An efficient and convenient procedure for the synthesis of thiazole derivatives from ?-haloketone, thiourea and substituted acetophenones using polyethylene glycol-400 as a green and recyclable solvent is described. Significant rate enhancement and improved yields have been observed.
Bhaskar S. Dawane; Baseer M. Shaikh; Namdev T. Khandare; Vinod T. Kamble; Santosh S. Chobe; Shankaraiah G. Konda
Efficient synthesis of [18F]trifluoromethane and its application in the synthesis of PET tracers.
A new strategy towards [(18)F]trifluoromethyl-containing compounds is developed. [(18)F]trifluoromethane is synthesised in a fast and efficient manner and subsequently used in the reaction with aldehydes and ketones forming [(18)F]trifluoromethyl carbinols in good yields. PMID:23563284
van der Born, Dion; Herscheid, J Koos D M; Orru, Romano V A; Vugts, Danielle J
Chemoselective alkane oxidation by superoxo-vanadium(V) in vanadosilicate molecular sieves.
Electron paramagnetic resonance (EPR) spectroscopy of reactive superoxo-vanadium(V) species in vanadosilicate molecular sieves (microporous VS-1 and mesoporous V-MCM-41) generated on contact with H2O2, tert-butyl hydroperoxide (TBHP), or (H2+O2) is reported for the first time. By suitable choice of the silicate structure, solvent, and oxidant, we could control the vanadium-(O2-*) bond (i.e., the V-O bond) covalency, the mode of O-O cleavage (in the superoxo species), and, therefore, chemoselectivity in the oxidation of n-hexane: Oxidation by TBHP over V-MCM-41, for example, yielded 27.2% of (n-hexanol+n-hexanal+n-hexanoic acid), among the highest chemoselectivities for oxidation of the terminal -CH3 in a linear paraffin reported to date. Over these vanadosilicates, oxidation of the primary C-H bond occurs only via a homolytic O-O bond cleavage; the secondary C-H bond oxidations may proceed via both the homo- and heterolytic O-O cleavage mechanisms. PMID:16471587
Shetti, Vasudev N; Rani, M Jansi; Srinivas, D; Ratnasamy, Paul
Two-photon fluorescence imaging of intracellular hydrogen peroxide with chemoselective fluorescent probes.
We present the application of two-photon fluorescence (TPF) imaging to monitor intracellular hydrogen peroxide (H?O?) production in brain cells. For selective imaging of H?O? over other reactive oxygen species, we employed small-molecule fluorescent probes that utilize a chemoselective boronate deprotection mechanism. Peroxyfluor-6 acetoxymethyl ester detects global cellular H?O? and mitochondria peroxy yellow 1 detects mitochondrial H?O?. Two-photon absorption cross sections for these H?O? probes are measured with a mode-locked Ti:sapphire laser in the wavelength range of 720 to 1040 nm. TPF imaging is demonstrated in the HT22 cell line to monitor both cytoplasmic H?O? and localized H?O? production in mitochondria. Endogenous cytoplasmic H?O? production is detected with TPF imaging in rat astrocytes modified with d-amino acid oxidase. The TPF H?O? imaging demonstrated that these chemoselective probes are powerful tools for the detection of intracellular H?O?. PMID:24084856
Guo, Hengchang; Aleyasin, Hossein; Howard, Scott S; Dickinson, Bryan C; Lin, Vivian S; Haskew-Layton, Renee E; Xu, Chris; Chen, Yu; Ratan, Rajiv R
The nodal response to chemoselection predicts the risk of recurrence following definitive chemoradiotherapy for pharyngeal cancer.
Abstract Conclusions: The poor response of neck tumors to induction chemotherapy (ICT) as chemoselection is related to a significantly worse prognosis, including higher risks of local recurrence and/or distant metastasis, after definitive chemoradiotherapy (CRT). Objectives: Neck dissection is frequently performed to treat residual lymph nodes after CRT for the purpose of locoregional control; however, the prognosis of patients with pathologically proven residual neck tumors is poor, and no methods for predicting unfavorable results before CRT have been established. Therefore, in the present study, we focused on the response of lymph nodes to ICT and its relationship with the prognosis among patients treated with chemoselection. Methods: We retrospectively reviewed a total of 27 oropharyngeal and 24 hypopharyngeal squamous cell carcinoma stage III/IV consecutive patients with cervical lymph node metastasis who exhibited a response of >50% in the primary tumor to ICT followed by concurrent definitive CRT. Results: The relapse-free survival of the patients who responded (partial response/complete response, PR/CR) to ICT was significantly superior to that of the patients who did not respond (stable disease, SD) to ICT (p = 0.008). PMID:25022795
Hanai, Nobuhiro; Ozawa, Taijiro; Hirakawa, Hitoshi; Suzuki, Hidenori; Fukuda, Yujiro; Hasegawa, Yasuhisa
A small molecule that could bind selectively to and then react chemoselectively with a non-enzyme protein in a complex biological fluid, such as blood, could have numerous practical applications. Herein, we report a family of designed stilbenes that selectively and covalently modify the prominent plasma protein transthyretin in preference to more than 4,000 other human plasma proteins. They react chemoselectively with only one of eight lysine {epsilon}-amino groups within transthyretin. The crystal structure confirms the expected binding orientation of the stilbene substructure and the anticipated conjugating amide bond. These covalent transthyretin kinetic stabilizers exhibit superior amyloid inhibition potency compared to their noncovalent counterparts, and they prevent cytotoxicity associated with amyloidogenesis. Though there are a few prodrugs that, upon metabolic activation, react with a cysteine residue inactivating a specific non-enzyme, we are unaware of designed small molecules that react with one lysine {epsilon}-amine within a specific non-enzyme protein in a complex biological fluid.
Choi, Sungwook; Connelly, Stephen; Reixach, Nat�lia; Wilson, Ian A.; Kelly, Jeffery W. (Scripps)
Facile and efficient one-pot synthesis of benzimidazoles using lanthanum chloride
Background We report the synthesis of benzimidazoles using lanthanum chloride as an efficient catalyst. One-pot synthesis of 2-substituted benzimidazole derivatives from o-phenylenediamine and a variety of aldehydes were developed under mild reaction conditions. Results We have examined the effect of different solvents using the same reaction conditions. The yield of the product varied with the nature of the solvents, and better conversion and easy isolation of products were found with acetonitrile. In a similar manner, the reaction with o-phenylenediamine and 3,4,5-trimethoxybenzaldehyde was carried out without any solvents. The observation shows that the reaction was not brought into completion, even after starting for a period of 9 h, and the reaction mixture showed a number of spots in thin-layer chromatography. Conclusions In conclusion, lanthanum chloride has been employed as a novel and efficient catalyst for the synthesis of benzimidazoles in good yields from o-phenylenediamine and a wide variety of aldehydes. All of the reactions were carried out in the presence of lanthanum chloride (10 mol%) in acetonitrile at room temperature.
Efficient Synthesis of N-Fmoc-Aminoalkoxy Pentafluorophenyl Carbonates: Application for the Synthesis of Oligopeptidyl Carbamates
N-Fmoc-?-Aminoalkoxy pentafluorophenyl carbonates have been synthesized through the reaction of N-Fmoc-?-aminoalkoxy carbonyl chloride with pentafluorophenol. The reaction was clean and high yielding, and the products have been fully characterized using infrared, NMR, and mass spectroscopy. Their utility as efficient building blocks for the preparation of N-Fmoc-oligopeptidyl carbamate esters and acids has been demonstrated. The method exemplifies a simple protocol for
Vommina V. Sureshbabu; H. P. Hemantha
Efficient synthesis of silver nanoparticles from Prosopis juliflora leaf extract and its antimicrobial activity using sewage
In this paper, aqueous extract of fresh leaves of Prosopis juliflora was used for the synthesis of silver (Ag) nanoparticles. UV-Vis spectroscopy studies were carried out to asses silver nanoparticles formation within 5 min, scanning electron microscopic was used to characterize shape of the Ag nanoparticles, X-ray diffraction analysis confirms the nanoparticles as crystalline silver and facecentered cubic type and Fourier transform infra-red assed that shows biomolecule compounds which are responsible for reduction and capping material of silver nanoparticles. The anti microbial activity of silver nanoparticle was performed using sewage. The approach of plant-mediated synthesis appears to be cost efficient, eco-friendly and easy methods.
Raja, K.; Saravanakumar, A.; Vijayakumar, R.
Thioester-isocyanides: versatile reagents for the synthesis of cycle-tail peptides.
A novel class of reagents, thioester isocyanides, have been prepared and applied in the synthesis of peptide macrocycles. The isocyanide part of the molecule is deployed in a multicomponent macrocyclization step. This step is followed by chemoselective peptide ligation at the thioester part of the macrocycle. Our method can now be used for rapid assembly and evaluation of cycle-tail peptides. PMID:22430393
Rotstein, Benjamin H; Winternheimer, David J; Yin, Lois M; Deber, Charles M; Yudin, Andrei K
Enantioselective total synthesis of marine diterpenoid clavulactone.
The key steps in the synthesis of clavulactone are formation of an enantiopure cyclopentane precursor by epoxide rearrangement and intramolecular carbonyl-ene reaction, construction of the 3,4-dihydro-2H-pyran ring by intermolecular hetero-Diels-Alder reaction, closure of the eleven-membered ring, and finally generation of the lactone functionality by chemoselective allylic C(sp(3))-H oxidation. PMID:22644725
Yang, Zhen-Yu; Liao, Hong-Ze; Sheng, Kang; Chen, Yong-Fei; Yao, Zhu-Jun
Total synthesis of lodopyridone.
A convergent total synthesis of the structurally unprecedented alkaloid lodopyridone was achieved using a cross-coupling of an iodopyridone fragment with a quinolinethiazolylstannane. Key features of the syntheses of the pentasubstituted 4-pyridone were a regioselective bromination of a 4-pyridone derived from kojic acid, a subsequent Cu-mediated introduction of the thioether, and a directed lithiation/iodination step. A chemoselective Negishi cross-coupling of a dibromothiazole and a quinolinylzinc reagent was used to assemble the chloroquinolinethiazol moiety. PMID:22909023
Burckhardt, Tobias; Harms, Klaus; Koert, Ulrich
The Efficient and Enantiospecific Total Synthesis of Cyclopenta[b]phenanthrenes Structurally-related to Neurosteroids
We report an efficient synthesis of cyclopenta[b]phenanthrenes functionalized at C-3 and C-8 from an optically pure Hajos-Parrish ketone. The key step is a neutral alumina catalyzed Michael addition of a Hajos-Parrish ketone derivative (4) to 1,7-octadien-3-one (2) in 98% yield. This Michael addition product went through Krapcho decarbomethoxylation, aldol condensation, lithium liquid ammonia reduction, Wacker oxidation and acid catalyzed cyclization to form cyclopenta[b]phenanthrene (1a) in 37% overall yield for the 7 steps.
Qian, Mingxing; Covey, Douglas F.
Efficient Utilization of Crude Glycerol as Fermentation Substrate in the Synthesis of Poly(3-hydroxybutyrate) Biopolymers
One refined and two crude glycerol (from biodiesel production) samples were utilized to produce poly(3-hydroxybutyrate) (PHB)\\u000a by Pseudomonas oleovorans NRRL B-14682. A batch culture fermentation protocol including 1% glycerol and an aeration rate of 3 standard liters per minute\\u000a proved best for PHB synthesis (av. yield�=�1.0���0.2�g\\/L at 48�h) and efficient glycerol utilization. PHB molecular weights\\u000a decreased as MeOH concentration increased.
Richard D. AshbyDaniel; Daniel K. Y. Solaiman; Gary D. Strahan
Poliovirus Requires a Precise 5? End for Efficient Positive-Strand RNA Synthesis
Poliovirus infectious RNA can be synthesized in vitro using phage DNA-dependent RNA-polymerases. These synthetic transcripts contain several extra nucleotides at the 5? end, which are deleted during replication to generate authentic viral genomes. We removed those 5?-end extra nucleotides utilizing a hammerhead ribozyme to produce transcripts with accurate 5? ends. These transcripts replicate substantially more rapidly in cell culture, demonstrating no lag before replication; they also replicate more efficiently in Xenopus laevis oocytes and in in vitro translation-replication cell extracts. In both systems, an exact 5? end is necessary for synthesis of positive-strand RNA but not negative-strand RNA.
Herold, Jens; Andino, Raul
Air-stable gold nanoparticles ligated by secondary phosphine oxides for the chemoselective hydrogenation of aldehydes: crucial role of the ligand.
The synthesis of air-stable and homogeneous gold nanoparticles (AuNPs) employing tert-butyl(naphthalen-1-yl)phosphine oxide as supporting ligand is described via NaBH4 reduction of a Au(I) precursor, [(tert-butyl(naphthalen-1-yl)phosphine oxide)AuCl]2. This highly reproducible and simple procedure furnishes small (1.24 � 0.16 nm), highly soluble nanoparticles that are found to be highly active catalysts for the hydrogenation of substituted aldehydes, giving high conversions and chemoselectivities for a wide variety of substrates. In addition to catalytic studies the role of the novel stabilizer in the remarkable activity and selectivity exhibited by this system was interrogated thoroughly using a wide range of techniques, including ATR FT-IR, HRMAS NMR, XPS, and EDX spectroscopy. In particular, isotopic labeling experiments enabled us to probe the coordination mode adopted by the SPO ligand bound to the nanoparticle surface by ATR FT-IR spectroscopy. In combination with a series of control experiments we speculate that the SPO ligand demonstrates ligand-metal cooperative effects and plays a seminal role in the heterolytic hydrogenation mechanism. PMID:24444462
Cano, Israel; Chapman, Andrew M; Urakawa, Atsushi; van Leeuwen, Piet W N M
Breaking the dichotomy of reactivity vs. chemoselectivity in catalytic SN1 reactions of alcohols.
The inability to decouple Lewis acid catalysis from undesirable Br�nsted acid catalysed side reactions when water or other protic functional groups are necessarily present has forced chemists to choose between powerful but harsh catalysts or poor but mild ones, a dichotomy that restricts the substrate scope of dehydrative transformations such as the direct SN1 reaction of alcohols. A systematic survey of Lewis and Br�nsted acids reveals that the strong non-hydrolyzable Lewis acid B(C6F5)3 leads to highly chemoselective alcohol substitution in the presence of acid-sensitive alkenes, protecting groups and other functional groups without the typical compromise in reaction rates, substrate scope and catalyst loading. PMID:24987941
Hellal, Malik; Falk, Florian C; Wolf, El�na; Dryzhakov, Marian; Moran, Joseph
Visible-light-induced chemoselective deboronative alkynylation under biomolecule-compatible conditions.
Here, we report a visible-light-induced deboronative alkynylation reaction, which is redox-neutral and works with primary, secondary and tertiary alkyl trifluoroborates or boronic acids to generate aryl, alkyl and silyl substituted alkynes. This reaction is highly chemoselective and performs well on substrates containing alkenes, alkynes, aldehydes, ketones, esters, nitriles, azides, aryl halides, alkyl halides, alcohols, and indoles, with no detectable occurrence of side reactions. The mechanism of this novel C(sp(3))-C(sp) bond coupling reaction was investigated by luminescence quenching, radical trapping, on-off light, and (13)C-isotopic-labeling experiments. This reaction can be performed in neutral aqueous conditions, and it is compatible with amino acids, nucleosides, oligosaccharides, nucleic acids, proteins, and cell lysates. PMID:24490981
Huang, Hanchu; Zhang, Guojin; Gong, Li; Zhang, Shuaiyan; Chen, Yiyun
Mechanistic Study of Chemoselectivity in Ni-Catalyzed Coupling Reactions between Azoles and Aryl Carboxylates.
Itami et al. recently reported the C-O electrophile-controlled chemoselectivity of Ni-catalyzed coupling reactions between azoles and esters: the decarbonylative C-H coupling product was generated with the aryl ester substrates, while C-H/C-O coupling product was generated with the phenol derivative substrates (such as phenyl pivalate). With the aid of DFT calculations (M06L/6-311+G(2d,p)-SDD//B3LYP/6-31G(d)-LANL2DZ), the present study systematically investigated the mechanism of the aforementioned chemoselective reactions. The decarbonylative C-H coupling mechanism involves oxidative addition of C(acyl)-O bond, base-promoted C-H activation of azole, CO migration, and reductive elimination steps (C-H/Decar mechanism). This mechanism is partially different from Itami's previous proposal (Decar/C-H mechanism) because the C-H activation step is unlikely to occur after the CO migration step. Meanwhile, C-H/C-O coupling reaction proceeds through oxidative addition of C(phenyl)-O bond, base-promoted C-H activation, and reductive elimination steps. It was found that the C-O electrophile significantly influences the overall energy demand of the decarbonylative C-H coupling mechanism, because the rate-determining step (i.e., CO migration) is sensitive to the steric effect of the acyl substituent. In contrast, in the C-H/C-O coupling mechanism, the release of the carboxylates occurs before the rate-determining step (i.e., base-promoted C-H activation), and thus the overall energy demand is almost independent of the acyl substituent. Accordingly, the decarbonylative C-H coupling product is favored for less-bulky group substituted C-O electrophiles (such as aryl ester), while C-H/C-O coupling product is predominant for bulky group substituted C-O electrophiles (such as phenyl pivalate). PMID:24823646
Lu, Qianqian; Yu, Haizhu; Fu, Yao
Efficient Synthesis of Eriodictyol from L-Tyrosine in Escherichia coli.
The health benefits of flavonoids for humans are increasingly attracting attention. Because the extraction of high-purity flavonoids from plants presents a major obstacle, interest has emerged in biosynthesizing them using microbial hosts. Eriodictyol is a flavonoid with anti-inflammatory and antioxidant activities. Its efficient synthesis has been hampered by two factors: the poor expression of cytochrome P450 and the low intracellular malonyl coenzyme A (malonyl-CoA) concentration in Escherichia coli. To address these issues, a truncated plant P450 flavonoid, flavonoid 3'-hydroxylase (tF3'H), was functionally expressed as a fusion protein with a truncated P450 reductase (tCPR) in E. coli. This allowed the engineered E. coli to produce eriodictyol from l-tyrosine by simultaneously coexpressing the fusion protein with tyrosine ammonia lyase (TAL), 4-coumarate-CoA ligase (4CL), chalcone synthase (CHS), and chalcone isomerase (CHI). In addition, metabolic engineering was employed to enhance the availability of malonyl-CoA so as to achieve a new metabolic balance and rebalance the relative expression of genes to enhance eriodictyol accumulation. This approach made the production of eriodictyol 203% higher than that in the control strain. By using these strategies, the production of eriodictyol from l-tyrosine reached 107 mg/liter. The present work offers an approach to the efficient synthesis of other hydroxylated flavonoids from l-tyrosine or even glucose in E. coli. PMID:24610848
Zhu, Saijie; Wu, Junjun; Du, Guocheng; Zhou, Jingwen; Chen, Jian
Sodium tetrachloroaurate(III) dihydrate-catalyzed efficient synthesis of 1,5-benzodiazepine and quinoxaline derivatives
Both 1,5-benzodiazepine and quinoxaline derivatives are important heterocycles in pharmaceuticals. We describe an efficient\\u000a and clean method for the synthesis of 1,5-benzodiazepines from o-phenylenediamine and ketones catalyzed by sodium tetrachloroaurate(III) dihydrate under mild conditions. The catalyst was\\u000a shown to be equally effective for the synthesis of quinoxalines from o-phenylenediamine and ?-bromo ketones under the similar reaction conditions. This method produced
Ren-xin Shi; Yun-kui Liu; Zhen-yuan Xu
Efficiency of software and algorithms of aperture synthesis in passive sonar devices on test and real signals
A SynApp program is developed for studying the algorithms of processing data obtained by arrays with a synthesized aperture\\u000a in passive sonar devices. Various synthesis algorithms are compared, and the best algorithm is chosen on the basis of particular\\u000a criteria. Inspection of program operation with signals obtained by a real array demonstrates the efficiency of synthesis with\\u000a the use of
O. Yu. Dashevskii; E. S. Nezhevenko
Sodium tetrachloroaurate(III) dihydrate-catalyzed efficient synthesis of 1,5-benzodiazepine and quinoxaline derivatives*
Both 1,5-benzodiazepine and quinoxaline derivatives are important heterocycles in pharmaceuticals. We describe an efficient and clean method for the synthesis of 1,5-benzodiazepines from o-phenylenediamine and ketones catalyzed by sodium tetrachloroaurate(III) dihydrate under mild conditions. The catalyst was shown to be equally effective for the synthesis of quinoxalines from o-phenylenediamine and ?-bromo ketones under the similar reaction conditions. This method produced good yields.
Shi, Ren-xin; Liu, Yun-kui; Xu, Zhen-yuan
Regio- and chemoselective bromination of 2,3-diarylcyclopent-2-en-1-ones.
The bromination of 2,3-diarylcyclopent-2-en-1-ones under various conditions has been studied. It was found that depending on the brominating reagent and nature of solvent the bromine atom can be introduced at the 4- or 5-position of the ethene "bridge", as well as into the aryl moieties. Aryl group bromination is accomplished with such reagents as molecular bromine, N-bromosuccinimide, or tetrabutylammonium tribromide. 5-Bromocyclopentenones with very high efficiency can be obtained by the reaction with copper(II) bromide in methanol, while 4-bromoketones are prepared in n-propyl acetate. The developed methods can be highly useful for the synthesis of bromo-substituted 2-cyclopenten-1-ones and their close analogues, which are important synthons in organic synthesis and for the preparation of a variety of useful substances. PMID:22924429
Shirinian, Valerii Z; Lonshakov, Dmitry V; Kachala, Vadim V; Zavarzin, Igor V; Shimkin, Alexey A; Lvov, Andrew G; Krayushkin, Mikhail M
Efficient synthesis of 3-O-thia-cPA and preliminary analysis of its biological activity toward autotaxin.
The efficient synthesis of 3-O-thia-cPAs (4a-d), sulfur analogues of cyclic phosphatidic acid (cPA), has been achieved. The key step of the synthesis is an intramolecular Arbuzov reaction to construct the cyclic thiophosphate moiety. The present synthetic route enables the synthesis of 4a-d in only four steps from the commercially available glycidol. Preliminary biological experiments showed that 4a-d exhibited a similar inhibitory effect on autotaxin (ATX) as original cPA. PMID:21676615
Tanaka, Ryo; Kato, Masaru; Suzuki, Takahiro; Nakazaki, Atsuo; Nozaki, Emi; Gotoh, Mari; Murakami-Murofushi, Kimiko; Kobayashi, Susumu
Synthesis and Evaluation of Tetramethylguanidinium-Polyethylenimine Polymers as Efficient Gene Delivery Vectors
Previously, we demonstrated that 6-(N,N,N?,N?-tetramethylguanidinium chloride)-hexanoyl-polyethylenimine (THP) polymers exhibited significantly enhanced transfection efficiency and cell viability. Here, in the present study, we have synthesized a series of N,N,N?,N?-tetramethylguanidinium-polyethylenimine (TP1-TP5) polymers via a single-step reaction involving peripheral primary amines of bPEI and varying amounts of 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU). These polymers were found to interact efficiently with negatively charged pDNA and formed stable complexes in the size range of ~240�450?nm. Acid-base titration profiles revealed improved buffering capacity of TP polymers as compared to bPEI. Transfection and cytotoxicity assays performed with TP/pDNA complexes on HEK293, CHO, and HeLa cells showed significantly higher transfection efficiency and cell viability with one of the complexes, TP2/pDNA complex, exhibited the highest transfection efficiency (~1.4�2.3-fold) outcompeting native bPEI and the commercially available transfection reagent, Lipofectamine 2000. Compared to previously reported THP polymers, the transfection efficiency of TP/pDNA complexes was found to be lower, as examined by flow cytometry. These results highlight the importance of the hydrophobic C-6 linker in THP polymers in forming compact nanostructures with pDNA, which might lead to efficient uptake and internalization of the complexes; however, the projected TP polymers offer an advantage of their rapid and economical one-step synthesis.
Mahato, Manohar; Yadav, Santosh; Kumar, Pradeep; Sharma, Ashwani Kumar
Mild and chemoselective lactone ring-opening with (TMS)ONa. Mechanistic studies and application to sweroside derivatives.
Mild and chemoselective opening of lactones with sodium trimethylsilanolate in high yields and aprotic solvents is described. Kinetic studies demonstrate that the B(Ac)2 mechanistic pathway is followed. Nucleophilic attack of silanolate onto the carbonyl of the lactone moiety is the rate-determining step. NaOH present as an impurity accelerates the reaction. The method was further applied to the base-sensitive and stable lactones derived from highly functionalized iridoid derivatives. PMID:24738692
Lemoine, Hugues; Markovi?, Dean; Deguin, Brigitte
Chemoselective N-heterocyclic carbene-catalyzed cross-benzoin reactions: importance of the fused ring in triazolium salts.
Morpholinone- and piperidinone-derived triazolium salts are shown to catalyze highly chemoselective cross-benzoin reactions between aliphatic and aromatic aldehydes. The reaction scope includes ortho-, meta-, and para-substituted benzaldehyde derivatives with a range of electron-donating and -withdrawing groups as well as branched and unbranched aliphatic aldehydes. Catalytic loadings as low as 5 mol % give excellent yields in these reactions (up to 99%). PMID:24809936
Langdon, Steven M; Wilde, Myron M D; Thai, Karen; Gravel, Michel
Diborylation of alkynyl MIDA boronates and sequential chemoselective Suzuki-Miyaura couplings: a formal carboborylation of alkynes.
Platinum-catalyzed diborylation of phenylethynyl MIDA boronate with Bpin-Bpin proceeds to yield 1,1,2-triboryl-2-phenylethene with two different classes of the boron functionalities. Sequentially, the obtained 1,1,2-triboryl-2-phenylethene are subjected to Suzuki-Miyaura coupling to introduce a series of aryl groups chemoselectively to afford 1,1-boryl-2,2-diarylethenes. PMID:24364421
Hyodo, Keita; Suetsugu, Masato; Nishihara, Yasushi
Solvent-controlled halo-selective selenylation of aryl halides catalyzed by Cu(II) supported on Al2O3. A general protocol for the synthesis of unsymmetrical organo mono- and bis-selenides.
Alumina-supported Cu(II) efficiently catalyzes selenylation of aryl iodides and aryl bromides by diaryl, dialkyl, and diheteroaryl diselenides in water and PEG-600, respectively, leading to a general route toward synthesis of unsymmetrical diaryl, aryl-alkyl, aryl-heteroaryl, and diheteroaryl selenides. A sequential reaction of bromoiodobenzene with one diaryl/diheteroaryl/dialkyl diselenide in water and another diaryl/diheteroaryl/dialkyl diselenide in PEG-600 in the second step produces unsymmetrical diaryl, diheteroaryl, or aryl-alkyl bis-selanyl benzene. A library of functionalized organo mono- and bis-selenides, including a potent biologically active molecule and a couple of analogues of bioactive selenides, were obtained in high yields by this protocol. The reactions are chemoselective and high yielding. The Cu-Al2O3 catalyst is recycled for seven runs without any appreciable loss of activity. PMID:23786642
Chatterjee, Tanmay; Ranu, Brindaban C
Design and Synthesis of Novel Block Copolymers for Efficient Opto-Electronic Applications
NASA Technical Reports Server (NTRS)
It has been predicted that nano-phase separated block copolymer systems containing electron rich donor blocks and electron deficient acceptor blocks may facilitate the charge carrier separation and migration in organic photovoltaic devices due to improved morphology in comparison to polymer blend system. This paper presents preliminary data describing the design and synthesis of a novel Donor-Bridge-Acceptor (D-B-A) block copolymer system for potential high efficient organic optoelectronic applications. Specifically, the donor block contains an electron donating alkyloxy derivatized polyphenylenevinylene (PPV), the acceptor block contains an electron withdrawing alkyl-sulfone derivatized polyphenylenevinylene (PPV), and the bridge block contains an electronically neutral non-conjugated aliphatic hydrocarbon chain. The key synthetic strategy includes the synthesis of each individual block first, then couple the blocks together. While the donor block stabilizes and facilitates the transport of the holes, the acceptor block stabilizes and facilitates the transport of the electrons, the bridge block is designed to hinder the probability of electron-hole recombination. Thus, improved charge separation and stability are expected with this system. In addition, charge migration toward electrodes may also be facilitated due to the potential nano-phase separated and highly ordered block copolymer ultra-structure.
Sun, Sam-Shajing; Fan, Zhen; Wang, Yiqing; Taft, Charles; Haliburton, James; Maaref, Shahin
Design, synthesis and biological studies of efficient multivalent melanotropin ligands: tools towards melanoma diagnosis and treatment
In order to achieve early detection and specific cancer treatment we propose the use of multivalent interactions in which a series of binding events leads to increased affinity and consequently to selectivity. Using melanotropin (MSH) ligands, our aim is to target melanoma cells, which overexpress melanocortin receptors. In this study, we report the design and efficient synthesis of new trivalent ligands bearing MSH ligands. Evaluation of these multimers on a cell model engineered to overexpress melanocortin 4 receptors (MC4R) showed up to a 350-fold increase in binding compared to the monomer, resulting in a trivalent construct with nanomolar affinity starting from a micromolar affinity ligand. Cyclic adenosine monophosphate (cAMP) production was also investigated leading to more insights into the effects of multivalent compounds on transduction mechanisms.
Brabez, Nabila; Lynch, Ronald M.; Xu, Liping; Gillies, Robert J.; Chassaing, Gerard; Lavielle, Solange; Hruby, Victor J.
Efficient assembly of threaded molecular machines for sequence-specific synthesis.
We report on an improved strategy for the preparation of artificial molecular machines that can pick up and assemble reactive groups in sequence by traveling along a track. In the new approach a preformed rotaxane synthon is attached to the end of an otherwise fully formed strand of building blocks. This "rotaxane-capping" protocol is significantly more efficient than the "final-step-threading" method employed previously and enables the synthesis of threaded molecular machines that operate on extended oligomer, and potentially polymer, tracks. The methodology is exemplified through the preparation of a machine that adds four amino acid building blocks from a strand in sequence, featuring up to 20-membered ring native chemical ligation transition states. PMID:24678971
De Bo, Guillaume; Kuschel, Sonja; Leigh, David A; Lewandowski, Bartosz; Papmeyer, Marcus; Ward, John W
Amino acid assisted templating synthesis of hierarchical zeolitic imidazolate framework-8 for efficient arsenate removal
We report the strategy of using the cationic surfactant cetyltrimethylammonium bromide (CTAB) and amino acid l-histidine (His) as co-templates to produce hierarchical ZIF-8 in an aqueous system at room temperature. The hierarchical ZIF-8 had both meso- and microporous structure, resulting in a high mesopore volume as well as specific surface area which can be controlled by the synthesis conditions. We put forward the hypothesis for the formation of a mesoporous structure and the enhancement of the porosity of ZIF-8 that the histidine plays a key role on the stabilization of CTAB micelles and avoiding the production of unexpected by-products therefore promotes the fabrication of pure phase ZIF-8 containing the mesopores interconnected with micropores. The prepared hierarchical ZIF-8 exhibited an excellent performance as a new kind of porous absorbent for efficient removal of the toxic arsenate.We report the strategy of using the cationic surfactant cetyltrimethylammonium bromide (CTAB) and amino acid l-histidine (His) as co-templates to produce hierarchical ZIF-8 in an aqueous system at room temperature. The hierarchical ZIF-8 had both meso- and microporous structure, resulting in a high mesopore volume as well as specific surface area which can be controlled by the synthesis conditions. We put forward the hypothesis for the formation of a mesoporous structure and the enhancement of the porosity of ZIF-8 that the histidine plays a key role on the stabilization of CTAB micelles and avoiding the production of unexpected by-products therefore promotes the fabrication of pure phase ZIF-8 containing the mesopores interconnected with micropores. The prepared hierarchical ZIF-8 exhibited an excellent performance as a new kind of porous absorbent for efficient removal of the toxic arsenate. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr04390h
Wu, Yi-Nan; Zhou, Meimei; Zhang, Bingru; Wu, Baozhen; Li, Jie; Qiao, Junlian; Guan, Xiaohong; Li, Fengting
A novel and efficient one-pot four-component tandem approach for the synthesis of pyran derivatives.
A series of new pyran derivatives are efficiently synthesized in a one-pot four-component tandem reaction via Suzuki coupling followed by a three-component reaction from readily available 4-bromobenzaldehyde, activated methylene compounds, and carbonyl compounds. Single crystal X-ray structure of the synthesized product is presented. The versatility and efficiency of the proposed methodology has been demonstrated in the synthesis of novel heterocyclic molecules. PMID:22729829
Zhang, Zhanyi; Xu, Yijing; Zheng, Jia; Li, Bin; Li, Yiqun
An efficient and clean synthesis of N-aryl azacycloalkanes from alkyl dihalides and aniline derivatives has been achieved using microwave irradiation in an aqueous potassium carbonate medium. The phase separation can simplify the product isolation and reduce usage of vol...
An efficient synthesis of novel fused cycloheptatrienes through Mn(II)-mediated formal intermolecular [2 + 2 + 2 + 1] cycloaddition.
A new method for manganous acetate tetrahydrate mediated formal intermolecular [2 + 2 + 2 + 1] cycloaddition was developed for the synthesis of fused cycloheptatriene derivatives from N-(acylmethyl)pyridinium iodides and naphthoquinone. This method provides an innovative route for the efficient and convenient construction of fused seven-membered carbocycles from simple starting materials. PMID:24564369
Shu, Wen-Ming; Ma, Jun-Rui; Yang, Yan; Wu, An-Xin
A remarkably efficient synthesis of pure cis-stilbenoid hydrocarbons using trans-dibromoalkenes via palladium catalysis.
A remarkably versatile synthesis of cis-stilbenoid hydrocarbons containing highly functionalized phenyl groups is developed via an efficient palladium-catalyzed coupling of aryl Grignard reagents with trans-1,2-dibromoalkenes (generally obtained via bromination of the corresponding dialkylacetylenes) in tetrahydrofuran. PMID:12475309
Rathore, Rajendra; Deselnicu, Mihaela I; Burns, Carrie L
Efficient Nazarov cyclization/Wagner-Meerwein rearrangement terminated by a Cu(II)-promoted oxidation: synthesis of 4-alkylidene cyclopentenones.
The discovery and elucidation of a new Nazarov cyclization/Wagner-Meerwein rearrangement/oxidation sequence is described that constitutes an efficient strategy for the synthesis of 4-alkylidene cyclopentenones. DFT computations and EPR experiments were conducted to gain further mechanistic insight into the reaction pathways. PMID:23436470
Leb�uf, David; Theiste, Eric; Gandon, Vincent; Daifuku, Stephanie L; Neidig, Michael L; Frontier, Alison J
Efficient Nazarov Cyclization/Wagner-Meerwein Rearrangement Terminated by a Cu(II)-Promoted Oxidation: Synthesis of 4-Alkylidene Cyclopentenones
The discovery and elucidation of a novel Nazarov cyclization/Wagner-Meerwein rearrangement/oxidation sequence is described, which constitutes an efficient strategy for the synthesis of 4-alkylidene cyclopentenones. DFT computations and EPR experiments were conducted to gain further mechanistic insight into the reaction pathways.
Leboeuf, David; Theiste, Eric; Gandon, Vincent; Daifuku, Stephanie L.; Neidig, Michael L.
Efficient One-Step Synthesis of C3Symmetrical Benzenoid Compounds Mediated by SOCl2\\/EtOH
An efficient one-step synthesis of branched functionalized benzenoid compounds from aryl methyl ketones mediated by SOCl2\\/EtOH is described; some novel C3-symmetrical molecules were prepared with satisfactory yields. The method enjoys short reaction time and simple operation, and avoids use of organometallic reagents.
Sanhu Zhao; Lina Kang; Haixia Ge; Feifei Yang; Chenlu Wang; Chang Li; Qiang Wang; Minggen Zhao
An Efficient One-Step Synthesis of C3-symmetrical Benzenoid Compounds Mediated by SOCl2 \\/ EtOH
An efficient one-step synthesis of branched functionalized benzenoid compounds from aryl methyl ketones mediated by SOCl2 \\/ EtOH is described; some novel C3-symmetrical molecules were prepared with satisfied yields. The method enjoys the short reaction time, simple operation and avoidance of using organometallic reagents.
Efficient synthesis of ?-enaminones and ?-enaminoesters catalyzed by gold (I)/silver (I) under solvent-free conditions.
An efficient method for the synthesis of ?-enaminones and ?-enaminoesters using a combination of [(PPh(3))AuCl]/AgOTf as catalyst has been developed. The reaction between 1,3-dicarbonyl compounds and primary amines was carried out under solvent-free conditions with low catalyst loading in good to excellent yields at room temperature. PMID:22395409
Zhang, Ming; Abdukader, Ablimit; Fu, Yong; Zhu, Chengjian
Polysulfide reagent in solid-phase synthesis of phosphorothioate oligonucleotides: greater than 99.8% sulfurization efficiency.
A solution of sulfur (0.1 M) and sodium sulfide (0.01M) in 3-picoline, referred to as polysulfide reagent, rapidly converts trialkyl and triaryl phosphite triesters to the corresponding phosphorothioate derivatives. Greater than 99.8% average stepwise sulfurization efficiency is obtained in the solid-phase synthesis of DNA and RNA phosphorothioate olgonucleotides via the phosphoramidite approach. PMID:16252666
Krotz, Achim H; Hang, Alice; Gorman, Dennis; Scozzari, Anthony N
An efficient, multicomponent approach for solvent-free synthesis of 2-amino-4H-chromene scaffold.
Solvent-free one-pot synthesis of 2-amino-4H-chromene scaffold is described in a very simple, efficient, and environmentally benign method using sodium carbonate as a cheap and non-toxic catalyst with up to excellent yields. PMID:20373141
Naimi-Jamal, M Reza; Mashkouri, Sara; Sharifi, Ali
Efficiency of microbial protein synthesis on red clover and ryegrass silages supplemented with barley by rumen simulation technique (RUSITEC)
Bacterial protein supply from the rumen is frequently low in animals fed on silage-based diets, partially because of the lack of rumen available sources of energy. An in vitro experiment was designed to determine the optimum rate of inclusion of rolled barley to optimise rumen efficiency of bacterial protein synthesis (EBPS) of diets comprising a typical ryegrass silage (GR; crude
G. Jaurena; J. M. Moorby; D. R. Davies
Formal synthesis of 7-methoxymitosene and synthesis of its analog via a key PtCl2-catalyzed cycloisomerization.
A formal synthesis of 7-methoxymitosene is achieved via a key platinum-catalyzed cycloisomerization. The precursor for the Pt catalysis, a fully functionalized benzene intermediate, was prepared via a regioselective electrophilic bromination followed by a chemoselective Sonogashira cross-coupling. It underwent the PtCl2-catalyzed cycloisomerization smoothly despite its hindered and highly electron-rich nature. Analogs of 7-methoxymitosene can be accessed in an expedient manner by following a similar synthetic sequence. PMID:22765272
Liu, Lianzhu; Wang, Yanzhao; Zhang, Liming
Formal Synthesis of 7-Methoxymitosene and Synthesis of its Analog via a Key PtCl2-Catalyzed Cycloisomerization
A formal synthesis of 7-methoxymitosene is achieved via a key platinum-catalyzed cycloisomerization. The precursor for the Pt catalysis, a fully functionalized benzene intermediate, was prepared via a regioselective electrophilic bromination followed by a chemoselective Sonogashira cross-coupling. It underwent the PtCl2-catalyzed cycloisomerization smoothly albeit its hindered and highly electron-rich nature. Analogs of 7-methoxymitosene can be accessed in an expedient manner by following a similar synthetic sequence.
Liu, Lianzhu; Wang, Yanzhao
A Highly Practical Copper(I)/TEMPO Catalyst System for Chemoselective Aerobic Oxidation of Primary Alcohols
Aerobic oxidation reactions have been the focus of considerable attention, but their use in mainstream organic chemistry has been constrained by limitations in their synthetic scope and by practical factors, such as the use of pure O2 as the oxidant or complex catalyst synthesis. Here, we report a new (bpy)CuI/TEMPO catalyst system that enables efficient and selective aerobic oxidation of a broad range of primary alcohols, including allylic, benzylic and aliphatic derivatives, to the corresponding aldehydes using readily available reagents, at room temperature with ambient air as the oxidant. The catalyst system is compatible with a wide range of functional groups and the high selectivity for 1� alcohols enables selective oxidation of diols that lack protecting groups.
Hoover, Jessica M.; Stahl, Shannon S.
Multi-component one-pot synthesis of the tumor-associated carbohydrate antigen Globo-H based on preactivation of thioglycosyl donors.
Two efficient routes for the rapid assembly of the tumor-associated carbohydrate antigen Globo-H hexasaccharide 2 by a preactivation based iterative one-pot strategy are reported. The first method involves the sequential coupling of four glycosyl building blocks, leading to the desired hexasaccharide in 47% overall yield in one-pot synthesis. Although model studies on constructing the challenging Gal-alpha-(1-4)-Gal linkage in Gb3 trisaccharide yielded the desired alpha linkage almost exclusively, a similar approach to assemble the hexasaccharide led to the formation of a significant amount of beta anomer. As an alternative, the second synthesis utilized three components in one pot with the Gal-alpha-(1-4)-Gal linkage preformed, producing the desired hexasaccharide in a similar overall yield as the four component approach. Both methods demonstrate that oligosaccharides containing alpha and beta linkages within the same molecule can be constructed in one pot via a preactivation based approach with higher glyco-assembly efficiencies than the automated solid-phase synthesis strategy. Furthermore, because glycosylations can be carried out independent of anomeric reactivities of donors, it is not necessary to differentiate anomeric reactivities of building blocks through extensive protective group adjustment for chemoselective glycosylation. This confers great flexibilities in the building block design, allowing matching of the donor with the acceptor, leading to improved overall yield. PMID:17658849
Wang, Zhen; Zhou, Luyuan; El-Boubbou, Kheireddine; Ye, Xin-shan; Huang, Xuefei
Stereoselective, nitro-Mannich/lactamisation cascades for the direct synthesis of heavily decorated 5-nitropiperidin-2-ones and related heterocycles.
A versatile nitro-Mannich/lactamisation cascade for the direct stereoselective synthesis of heavily decorated 5-nitropiperidin-2-ones and related heterocycles has been developed. A highly enantioenriched substituted 5-nitropiperidin-2-one was synthesised in a four component one-pot reaction combining an enantioselective organocatalytic Michael addition with the diastereoselective nitro-Mannich/lactamisation cascade. Protodenitration and chemoselective reductive manipulation of the heterocycles was used to install contiguous and fully substituted stereocentres in the synthesis of substituted piperidines. PMID:22563355
Jakubec, Pavol; Cockfield, Dane M; Helliwell, Madeleine; Raftery, James; Dixon, Darren J
Stereoselective, nitro-Mannich/lactamisation cascades for the direct synthesis of heavily decorated 5-nitropiperidin-2-ones and related heterocycles
Summary A versatile nitro-Mannich/lactamisation cascade for the direct stereoselective synthesis of heavily decorated 5-nitropiperidin-2-ones and related heterocycles has been developed. A highly enantioenriched substituted 5-nitropiperidin-2-one was synthesised in a four component one-pot reaction combining an enantioselective organocatalytic Michael addition with the diastereoselective nitro-Mannich/lactamisation cascade. Protodenitration and chemoselective reductive manipulation of the heterocycles was used to install contiguous and fully substituted stereocentres in the synthesis of substituted piperidines.
Jakubec, Pavol; Cockfield, Dane M; Helliwell, Madeleine; Raftery, James
Initiating nucleotide identity determines efficiency of RNA synthesis from 6S RNA templates in Bacillus subtilis but not Escherichia coli
The 6S RNA is a non-coding small RNA that binds within the active site of housekeeping forms of RNA polymerases (e.g. E?70 in Escherichia coli, E?A in Bacillus subtilis) and regulates transcription. Efficient release of RNA polymerase from 6S RNA regulation during outgrowth from stationary phase is dependent on use of 6S RNA as a template to generate a product RNA (pRNA). Interestingly, B. subtilis has two 6S RNAs, 6S-1 and 6S-2, but only 6S-1 RNA appears to be used efficiently as a template for pRNA synthesis during outgrowth. Here, we demonstrate that the identity of the initiating nucleotide is particularly important for the B. subtilis RNA polymerase to use RNA templates. Specifically, initiation with guanosine triphosphate (GTP) is required for efficient pRNA synthesis, providing mechanistic insight into why 6S-2 RNA does not support robust pRNA synthesis as it initiates with adenosine triphosphate (ATP). Intriguingly, E. coli RNA polymerase does not have a strong preference for initiating nucleotide identity. These observations highlight an important difference in biochemical properties of B. subtilis and E. coli RNA polymerases, specifically in their ability to use RNA templates efficiently, which also may reflect the differences in GTP and ATP metabolism in these two organisms.
Cabrera-Ostertag, Ignacio J.; Cavanagh, Amy T.; Wassarman, Karen M.
Rapid and highly efficient trimethylsilylation of alcohols and phenols with hexamethyldisilazane (HMDS) catalyzed by reusable zirconyl triflate, [ZrO(OTf) 2
In this paper, rapid and efficient trimethylsilylation of alcohols and phenols with hexamethyldisilazane in the presence of catalytic amounts of ZrO(OTf)2 is reported. Primary, secondary and tertiary alcohols as well as phenols were efficiently converted to their corresponding TMS ethers in short reaction times at room temperature. It is noteworthy that this method can be used for chemoselective silylation of
Majid Moghadam; Shahram Tangestaninejad; Valiollah Mirkhani; Iraj Mohammadpoor-Baltork; Shahin Chahardahcheric; Ziba Tavakoli
Towards the rational design of efficient organic structure-directing agents for zeolite synthesis.
Zeolites are crystalline microporous materials with application in diverse fields, especially in catalysis. The ability to prepare zeolites with targeted physicochemical properties for a specific catalytic application is a matter of great interest, because it allows the efficiency of the entire chemical process to be increased (higher product yields, lower undesired by-products, less energy consumption, and cost savings, etc). Nevertheless, directing the zeolite crystallization towards the material with the desired framework topology, crystal size, or chemical composition is not an easy task, since several variables influence the nucleation and crystallization processes. The combination of accumulated knowledge, rationalization, and innovation has allowed the synthesis of unique zeolitic structures in the last few years. This is especially true in terms of the design of organic and inorganic structure-directing agents (SDAs). In this Minireview we will present the rationale we have followed in our studies to synthesize new zeolite structures, while putting this in perspective with the advances made by other researchers of the zeolite community. PMID:24115577
Moliner, Manuel; Rey, Fernando; Corma, Avelino
Efficient synthesis of mibefradil analogues: an insight into in vitro stability.
This article describes the synthesis and biological evaluation of a chemical library of mibefradil analogues to investigate the effect of structural modification on in vitro stability. The construction of the dihydrobenzopyran structure in mibefradil derivatives 2 was achieved through two efficient approaches based on a diastereoselective intermolecular Reformatsky reaction and an intramolecular carbonyl-ene cyclization. In particular, the second strategy through the intramolecular carbonyl-ene reaction led to the formation of a key intermediate 3 in a short and highly stereoselective way, which has allowed for practical and convenient preparation of analogues 2. Using this protocol, we could obtain 22 new mibefradil analogues 2, which were biologically tested for in vitro efficacies against T-type calcium channels and metabolic stabilities. Among the synthesized compounds, we found that analogue 2aa containing a dihydrobenzopyran ring and a secondary amine linker showed high % remaining activities of the tested CYP enzymes retaining the excellent T-type calcium channel blocking activity. These findings indicated that the structural modification of 1 was effective for improving in vitro stability, i.e., reducing CYP inhibition and metabolic degradation. PMID:24964394
Lee, Ji Eun; Kwon, Tae Hui; Gu, Su Jin; Lee, Duck-Hyung; Kim, B Moon; Lee, Jae Yeol; Lee, Jae Kyun; Seo, Seon Hee; Pae, Ae Nim; Keum, Gyochang; Cho, Yong Seo; Min, Sun-Joon
Recent advances in the chemoselective reduction of functional groups mediated by samarium(II) iodide: a single electron transfer approach.
Recently, samarium(II) iodide reductants have emerged as powerful single electron donors for the highly chemoselective reduction of common functional groups. Complete control of the product formation can be achieved on the basis of a judicious choice of a Sm(II) complex/proton donor couple, even in the presence of extremely sensitive functionalities (iodides, aldehydes). In most cases, the reductions are governed by thermodynamic control of the first electron transfer, which opens up new prospects for unprecedented transformations via radical intermediates under mild regio-, chemo- and diastereoselective conditions that are fully orthogonal to hydrogenation or metal-hydride mediated processes. PMID:24013846
Szostak, Michal; Spain, Malcolm; Procter, David J
Efficient Synthesis of Poly(hydroxyethyl Methacrylate)-b-Poly(dimethylaminoethyl Methacrylate) Block Copolymer by Atom Transfer Radical Polymerization.
Polymers containing hydroxyethyl methacrylate (HEMA) and dimethylaminoethyl methacrylate (DMAEMA) have found wide applications in areas such as bioseparation, tissue engineering and controlled drug delivery. The controlled synthesis of block copolymers of PDMAEMA-b-PHEMA from PDMAEMA macroinitiator by atom transfer radical polymerization (ATRP), however, has not been successful due to the loss of chain end functionality during polymerization. We report an ATRP system that affords efficient chain extension from PDMAEMA to HEMA using Cu(0)/1,1,4,7,10,10-hexamethyltriethylenetetramine as the catalyst, 2-chloropropionitrile as the initiator in methanol at room temperature. A clear peak shift in the gel permeation chromatography trace towards shorter elution times indicates chain growth on HEMA addition. The chain end functionalities of PDMAEMA are thus retained and can be used to efficiently initiate chain extension reaction of HEMA. This new synthetic route opens new possibilities for the synthesis of pH- and temperature-responsive systems containing DMAEMA.
Tang, Wei; Loo, Yueh-Lin
An Efficient Solution-Phase Synthesis of 4,5,7-Trisubstituted Pyrrolo[3,2-d]pyrimidines
We have developed an efficient and robust route to synthesize 4,5,7-trisubstituted pyrrolo[3,2-d]pyrimidines as potent kinase inhibitors. This solution-phase synthesis features a SNAr substitution reaction, cross-coupling reaction, one-pot reduction/reductive amination and N-alkylation reaction. These reactions occur rapidly with high yields and have broad substrate scopes. A variety of groups can be selectively introduced into the N5 and C7 positions of 4,5,7-trisubstituted pyrrolopyrimidines at a late stage of the synthesis, thereby providing a highly efficient approach to explore the structure-activity relationships of pyrrolopyrimidine derivatives. Four synthetic analogs have been profiled against a panel of 48 kinases and a new and selective FLT3 inhibitor 9 is identified.
Zhang, Weihe; Liu, Jing; Stashko, Michael A.; Wang, Xiaodong
PEG-embedded KBr3: A recyclable catalyst for multicomponent coupling reaction for the efficient synthesis of functionalized piperidines
Summary PEG-embedded potassium tribromide ([K+PEG]Br3 ?) was found to be an efficient and recyclable catalyst for the synthesis of functionalized piperidines in high yields in a one step, three component coupling between aldehyde, amine and ?-keto ester. At the end of the reaction the [K+PEG]Br3 ? was readily regenerated from the reaction mixture by treating the residue containing [K+PEG]Br? with molecular bromine.
Verma, Sanny
An Efficient Total Synthesis of a Potent Anti-Inflammatory Agent, Benzocamphorin F, and Its Anti-Inflammatory Activity
A naturally occurring enynyl-benzenoid, benzocamphorin F (1), from the edible fungus Taiwanofungus camphoratus (Antrodia camphorata) was characterized by comprehensive spectral analysis. It displays anti-inflammatory bioactivity and is valuable for further biological studies. The present study is the first total synthesis of benzocamphorin F and the developed strategy described is a more efficient procedure that allowe the large-scale production of benzocamphorin F for further research of the biological activity both in vitro and in vivo.
Liao, Yu-Ren; Kuo, Ping-Chung; Liang, Jun-Weil; Shen, Yuh-Chiang; Wu, Tian-Shung
Solvent-Free Green and Efficient One-Pot Synthesis of Dihydropyrano[3,2-c]chromene Derivatives
A rapid, clean, and highly efficient method for synthesis of dihydropyrano[3,2-c]chromene derivatives by one-pot, three-component condensation of aromatic aldehydes, malononitrile, and 4-hydroxycoumarin using DABCO as catalyst in solvent-free neat conditions is described. The present method has the advantages of mild reaction conditions, short reaction times, easy isolation of products, and excellent yields.
Jain, Shubha; Rajguru, Deepika; Keshwal, Balwant S.; Acharya, Aman D.
Solvent-Free Green and Efficient One-Pot Synthesis of Dihydropyrano[3,2-c]chromene Derivatives.
A rapid, clean, and highly efficient method for synthesis of dihydropyrano[3,2-c]chromene derivatives by one-pot, three-component condensation of aromatic aldehydes, malononitrile, and 4-hydroxycoumarin using DABCO as catalyst in solvent-free neat conditions is described. The present method has the advantages of mild reaction conditions, short reaction times, easy isolation of products, and excellent yields. PMID:24282643
Jain, Shubha; Rajguru, Deepika; Keshwal, Balwant S; Acharya, Aman D
Efficient catalyst-free four-component synthesis of novel ?-aminoethers mediated by a Mannich type reaction.
Herein, it is provided an efficient and one-pot procedure for the synthesis of novel and diversely substituted ?-aminoethers in good yields through a four-component process by treatment of benzylamines with polyformaldehyde and activated alkenes in aliphatic alcohols acting both as solvent and as etherificant agents. Reactions proceeded via a Mannich-type reaction, where the formation of iminium ions and aminals was identified as the key intermediates to obtain the target products. PMID:23167924
Abonia, Rodrigo; Castillo, Juan; Insuasty, Braulio; Quiroga, Jairo; Nogueras, Manuel; Cobo, Justo
An efficient synthesis of benzodiazepinyl phosphonates as clostripain inhibitors via FeCl3 catalyzed four-component reaction.
A novel one-pot route for the synthesis of benzodiazepinyl phosphonates (BDPs) has been achieved. FeCl(3) efficiently catalyzed four-component condensation of diamines, acetone and phosphites in the presence of molecular sieves to furnish BDPs as novel chemical entities with good yield. The synthesized BDPs have shown significant protease inhibition activity against clostripain, a disease model for gas gangrene, suggesting that these novel chemical entities could be further explored as cysteine protease inhibitors. PMID:21584307
Bhattacharya, Asish K; Rana, Kalpeshkumar C; Raut, Dnyaneshwar S; Mhaindarkar, Vaibhav P; Khan, Mohamad I
Facile and efficient Lewis acid catalyzed synthesis of an asymmetric tetrazine useful for bio-orthogonal click chemistry applications
Bio-orthogonal tetrazine click reactions have recently attracted significant interest for applications spanning biological imaging, cancer targeting, and biomaterials science. Here, we report a simple and efficient two-step scheme for the synthesis of an asymmetric tetrazine molecule containing a carboxylic acid handle for subsequent macromolecular conjugation. Yields as high as 75% were achieved using as little as 0.005 equivalents of nickel triflate catalyst, which is a significant improvement over previous methodologies.
Alge, Daniel L.; Donohue, Dillon F.; Anseth, Kristi S.
One-pot hydrazide-based native chemical ligation for efficient chemical synthesis and structure determination of toxin Mambalgin-1.
An efficient one-pot chemical synthesis of snake venom toxin Mambalgin-1 was achieved using an azide-switch strategy combined with hydrazide-based native chemical ligation. Synthetic Mambalgin-1 exhibited a well-defined structure after sequential folding in vitro. NMR spectroscopy revealed a three-finger toxin family structure, and the synthetic toxin inhibited human acid-sensing ion channel 1a. PMID:24619065
Pan, Man; He, Yao; Wen, Ming; Wu, Fangming; Sun, Demeng; Li, Sijian; Zhang, Longhua; Li, Yiming; Tian, Changlin
A one-pot synthesis of 1,2,4,5-tetraarylimidazoles using molecular iodine as an efficient catalyst
Molecular iodine is a cheap, nontoxic catalyst, which acts as an efficient catalyst for the synthesis of 1,2,4,5-tetraarylimidazoles using benzoin, an aromatic aldehyde and an amine in the presence of ammonium acetate. The advantage of this method is the direct use of benzoin, which is transformed into benzil in situ and condenses further to generate the imidazole in a one-pot
Mazaahir Kidwai; Poonam Mothsra
Efficient synthesis of fluorophosphonylated alkyles by ring-opening reaction of cyclic sulfates.
Ring-opening reactions of functionalized 1,2-cyclic sulfates and oxetanes with the phosphonodifluoromethyl carbanion are reported. This approach allows an easy access to fluorinated beta-hydroxyphosphonates that are building blocks in the synthesis of acyclic nucleosides. Synthesis of precursors of nucleoside phosphorylase inhibitors from these alcohols is described. PMID:18666773
Diab, Sonia Amel; Sene, Aboubacary; Pfund, Emmanuel; Lequeux, Thierry
Efficient Example-Based Painting and Synthesis of 2D Directional Texture
We present a new method for converting a photo or image to a synthesized painting following the painting style of an example painting. Treating painting styles of brush strokes as sample textures, we reduce the problem of learning an example painting to a texture synthesis problem. The proposed method uses a hierarchical patch-based approach to the synthesis of directional textures.
Bin Wang; Wenping Wang; Huaiping Yang; Jia-guang Sun
Metal-Free, Efficient Oxyfluorination of Olefins for the Synthesis of ?-Fluoroketones.
A novel oxyfluorination of olefin reactions has been developed. The reactions involve a metal-free and green catalytic system for the synthesis of ?-fluoroketones which is an important building block for organic synthesis. Moreover, this reaction system exhibits great functional group tolerance. PMID:24901370
Yang, Qiang; Mao, Liu-Liang; Yang, Bin; Yang, Shang-Dong
Argifin; efficient solid phase total synthesis and evalution of analogues of acyclic peptide
An effective solid phase synthesis of Argifin, providing subsequent access to effective synthesis of analogues, was developed in 13% overall yield, as well as elucidating structure�activity relationships. The novel acyclic peptide 18b, prepared from a synthetic intermediate of Argifin, was found to be 70 times more potent as an inhibitor of Serratia marcescens chitinases B than Argifin itself
Toshiaki Sunazuka; Akihiro Sugawara; Kanami Iguchi; Tomoyasu Hirose; Kenichiro Nagai; Yoshihiko Noguchi; Yoshifumi Saito; Tsuyoshi Yamamoto; Hideaki Ui; Hiroaki Gouda; Kazuro Shiomi; Takeshi Watanabe; Satoshi ?mura
Reaction between triphenylphosphine and aromatic amines in the presence of diethyl azodicarboxylate: an efficient synthesis of aryliminophosphoranes under neutral and mild conditions
An efficient synthesis of aryliminophosphoranes is described. A mixture of an aromatic amine, diethyl azodicarboxylate and triphenylphosphine undergo a Mitsonobu type reaction at ambient temperature in dry dichloromethane to afford aryliminophosphoranes in excellent yields.
Mehdi Adib; Ehsan Sheikhi; Azadeh Deljoush
A novel one-step efficient method for the synthesis of tetrahydroindoles from 1-(1-pyrrolidino)cyclohexene and chloropyruvates
A highly efficient, one-step, versatile method for the synthesis of tetrahydroindoles has been developed on the basis of new ring formation in the reactions of 1-(1-pyrrolidino)cyclohexene with chloropyruvates.
Vakhid A. Mamedov; Nataliya A. Zhukova; Aidar T. Gubaidullin; Rustem A. Isanov
Direct formation of small Cu2O nanocubes, octahedra, and octapods for efficient synthesis of triazoles.
In most studies describing the preparation of Cu2O crystals of various morphologies, the particle sizes are normally hundreds of nanometers to micrometers due to rapid particle growth, so they are not exactly nanocrystals. Here we report surfactant-free formation of sub-100 nm Cu2O nanocrystals with systematic shape evolution from cubic to octahedral structures by preparing an aqueous mixture of Cu(OAc)2, NaOH, and N2H4 solution. Adjustment of the hydrazine volume enables the particle shape control. Uniform nanocubes and octahedra were synthesized with edge lengths of 37 and 67 nm, respectively. Novel Cu2O octapods with an edge length of 135 nm were also produced by mixing CuCl2 solution, SDS surfactant, NaOH solution, and NH2OH�HCl reductant solution. All of them are nearly the smallest Cu2O nanocrystals of the same shapes ever reported. These small cubes, octahedra, and octapods were employed as catalysts in the direct synthesis of 1,2,3-triazoles from the reaction of alkynes, organic halides, and NaN3 at 55 �C. All of them displayed high product yields in short reaction times. The octahedra enclosed by the {111} facets are the best catalysts, and can catalyze this cycloaddition reaction with high yields in just 2 h when different alkynes were used to make diverse triazole products. Hence, the small Cu2O particles provide time-saving, energy-efficient, and high product yield benefits to organocatalysis. PMID:24947435
Tsai, Ya-Huei; Chanda, Kaushik; Chu, Yi-Ting; Chiu, Chun-Ya; Huang, Michael H
Accelerated chemical synthesis of peptides and small proteins
The chemical synthesis of peptides and small proteins is a powerful complementary strategy to recombinant protein overexpression and is widely used in structural biology, immunology, protein engineering, and biomedical research. Despite considerable improvements in the fidelity of peptide chain assembly, side-chain protection, and postsynthesis analysis, a limiting factor in accessing polypeptides containing greater than 50 residues remains the time taken for chain assembly. The ultimate goal of this work is to establish highly efficient chemical procedures that achieve chain-assembly rates of approximately 10�15 residues per hour, thus underpinning the rapid chemical synthesis of long polypeptides and proteins, including cytokines, growth factors, protein domains, and small enzymes. Here we report Boc chemistry that employs O-(7-azabenzotriazol-1-yl)-N,N,N?,N?-tetramethyluronium hexafluorophosphate (HATU)/dimethyl sulfoxide in situ neutralization as the coupling agent and incorporates a protected amino acid residue every 5 min to produce peptides of good quality. This rapid coupling chemistry was successfully demonstrated by synthesizing several small to medium peptides, including the �difficult� C-terminal sequence of HIV-1 proteinase (residues 81�99); fragment 65�74 of the acyl carrier protein; conotoxin PnIA(A10L), a potent neuronal nicotinic receptor antagonist; and the pro-inflammatory chemotactic protein CP10, an 88-residue protein, by means of native chemical ligation. The benefits of this approach include enhanced ability to identify and characterize �difficult couplings,� rapid access to peptides for biological and structure�activity studies, and accelerated synthesis of tailored large peptide segments (<50 residues) for use in chemoselective ligation methods.
Miranda, Les P.; Alewood, Paul F.
Fluorous ligand capture (FLC): a chemoselective solution-phase strategy for isolating 99mTc-labelled compounds in high effective specific activity.
A new approach for preparing (99m)Tc-labelled compounds in high effective specific activity was developed by utilizing a novel fluorous ligand capture (FLC) agent and a chemoselective filtration strategy. This paradigm eliminates the need to use HPLC to obtain technetium(I) based molecular imaging probes free from residual precursor. PMID:21625674
Hicks, Justin W; Harrington, Laura E; Valliant, John F
Highly chemoselective 2,4,5-triaryl-1,3-dioxolane formation from intermolecular 1,3-dipolar addition of carbonyl ylide with aryl aldehydes.
[reaction: see text] Rhodium(II) acetate catalyzed 1,3-dipolar cycloaddition of methyl phenyldiazoacetate with a mixture of electron-rich and electron-deficient aryl aldehydes gave 1,3-dioxolanes in high yield with excellent chemoselectivity. PMID:15330590
Lu, Chong-Dao; Chen, Zhi-Yong; Liu, Hui; Hu, Wen-Hao; Mi, Ai-Qiao
Acylation of Grignard reagents mediated by N-methylpyrrolidone: a remarkable selectivity for the synthesis of ketones.
An efficient user-friendly method of acylation of Grignard reagents to selectively synthesize ketones is presented, which is assisted by simple amides such as NMP, or DMF. The present chemoselective method tolerates a variety of functional groups such as ketone, ester, nitrile and other functional groups. PMID:21706089
Gowda, Maravanhalli Sidde; Pande, Sushanth Sudhir; Ramakrishna, Ramesha Andagar; Prabhu, Kandikere Ramaiah
Scalable and chromatography-free synthesis of 2-(2-formylalkyl)arenecarboxylic acid derivatives through the supramolecularly controlled hydroformylation of vinylarene-2-carboxylic acids.
This protocol describes how to prepare 2-(2-formylalkyl)-arenecarboxylic acid derivatives, common building blocks for the synthesis of various valuable chemicals (e.g., anti-obesity and Alzheimer's disease treatment pharmaceuticals), by using the fully regioselective hydroformylation of vinyl arene derivatives. This catalytic reaction proceeds cleanly with 100% regioselectivity and chemoselectivity. The procedure is reliably scalable and can be efficiently conducted on a multigram scale. The analytically pure product is easily isolated with a nearly quantitative yield by using a simple acid-base extraction workup and avoids any tedious chromatography. This protocol details the synthesis of a bisphosphite ligand (L1) that is a pivotal element of the catalytic system used, Rh(acac)(CO)2 with ligand L1, starting from commercial building blocks. The protocol also describes a general procedure for the preparative hydroformylation of vinylarene-2-carboxylic acid derivatives to 2-formylalkylarene products, providing a representative example for the hydroformylation of 2-vinylbenzoic acid (1a) to 2-(3-oxopropane)-benzoic acid (2a). The synthesis of L1 (six chemical reactions) uses 2-nitrophenylhydrazine, 4-benzyloxybenzoylchloride and (S)-binol, and takes 5-7 working days. The actual hydroformylation reaction of each vinyl arene derivative takes ?4 h of active effort over a period of 1-3 d. PMID:24762785
Dydio, Pawe?; Reek, Joost N H
I. Development of Metal-Mediated SPOT-Synthesis Methods for the Efficient Construction of Small-Molecule Macroarrays. II. Design and Synthesis of Novel Bacterial Biofilm Inhibitors
I. The use of small molecule probes to explore biological phenomena has become a valuable tool in chemical biology. As a result, methods that permit the rapid synthesis and biological evaluation of such compounds are highly sought-after. The small molecule macroarray represents one such approach for the synthesis and identification of novel bioactive agents. Macroarrays are readily constructed via the SPOT-synthesis technique on planar cellulose membranes, yielding spatially addressed libraries of �10-1000 unique compounds. We sought to expand the arsenal of chemical reactions compatible with this solid-phase platform, and developed highly efficient SPOT-synthesis protocols for the Mizoroki-Heck, Suzuki-Miyaura, and copper-catalyzed azide-alkyne cycloaddition reaction. We demonstrated that these metal-mediated reactions can be implemented, either individually or sequentially, for the efficient construction of small molecules in high purity on rapid time scales. Utilizing these powerful C-C and C-N bond forming coupling reactions, we constructed a series of macroarrays based on novel stilbene, phenyl-naphthalene, and triazole scaliblds. Subsequent biological testing of the stilbene and phenyl-naphthalene libraries revealed several potent antagonists and agonists, respectively, of the quorum sensing (QS) receptor LuxR in Vibrio fischeri. II. Bacteria living within biofilms are notorious for their resistance to known antibiotic agents, and constitute a major human health threat. Methods to attenuate biofilm growth would have a significant impact on the management of bacterial infections. Despite intense research efforts, small molecules capable of either inhibiting or dispersing biolilms remain scarce. We utilized natural products with purported anti-biofilm or QS inhibitory activity as sources of structural insight to guide the synthesis of novel biofilm modulators with improved activities. These studies revealed 2-aminobenzimidazole derivatives as highly potent biofilm inhibitors and dispersers in the opportunistic pathogen Pseudomonas aeruginosa. Studies of second-generation 2-aminobenzimidazoles revealed important structure-activity relationships that guided the design of yet more potent analogs. These compounds are amongst the most potent inhibitors of biofilm formation in wild-type P. aeruginosa to be reported. Mechanistic studies of the most active compounds suggest that QS inhibition is one pathway by which 2-aminobenzimidazoles modulate biofilm growth.
Frei, Reto
An iminophosphorane-mediated efficient synthesis of the alkaloid eudistomin U of marine origin
The first synthesis of the alkaloid eudistomin U, by a four-step sequence is described. The key step, formation of the ?-carboline ring, involves a tandem aza Wittig \\/ electrocyclic ring closure process.
Pedro Molina; Pilar M. Fresneda; Sagrario Garc�a-Zafra
Efficient Synthesis of Suitably Protected ?-Difluoroalanine and ?-Difluorothreonine from L-Ascorbic Acid
Fluorinated amino acids are useful building blocks for the preparation of biologically active peptides and peptidomimetics with increased metabolic stability. We report here the synthesis of two fluorinated amino acids, ?-difluoroalanine and ?-difluorothreonine as analogs of Ser and Thr, respectively. These compounds were suitably protected for Fmoc-based solid phase peptide synthesis. Once incorporated into peptides, they may serve as alternative substrates or inhibitors of lantibiotic synthetases that post-translationally dehydrate Ser and Thr residues to dehydroalanine and dehydrobutyrine, respectively.
Li, Gongyong; van der Donk, Wilfred A.
Efficient Synthesis of Secondary Alkyl Fluorides via Suzuki Cross-Coupling Reaction of 1-Halo-1-fluoroalkanes.
Organofluorine compounds have found extensive applications in various areas of science. Consequently, the development of new efficient and selective methods for their synthesis is an important goal in organic chemistry. Here, we present the first Suzuki cross-coupling reaction which utilizes dihalo compounds for the preparation of secondary alkyl fluorides. Namely, an unprecedented use of simple 1-halo-1-fluoroalkanes as electrophiles in Csp(3)-Csp(3) and Csp(3)-Csp(2) cross-couplings allows for the formal site-selective incorporation of F-group in the alkyl chain with no adjacent activating functional groups. Highly effective approach to the electrophilic substrates, 1-halo-1-fluoroalkanes, via iododecarboxylation of the corresponding ?-fluorocarboxylic acids is also presented. The conceptually new route to organofluorides was used for the facile preparation of biomedically valuable compounds. In addition, we demonstrated that an asymmetric version of the developed reaction for the stereoconvergent synthesis of chiral secondary alkyl fluorides is feasible. PMID:24958322
Jiang, Xiaojian; Sakthivel, Sekarpandi; Kulbitski, Kseniya; Nisnevich, Gennady; Gandelman, Mark
One-pot gold-catalyzed synthesis of azepino[1,2-a]indoles.
Indoles from scratch: A gold(I)/N-heterocyclic carbene complex (IPr=1,3-di(isopropylphenyl)imidazol-2-ylidene) was found to be particularly effective as a catalyst, enabling the one-pot synthesis of tricyclic azepinoindoles by an unprecedented cascade reaction. Readily available substrates, high chemoselectivity, good yields, and water as the only stoichiometric by-product are some of the main advantages of this method. PMID:22945878
Cera, Gianpiero; Piscitelli, Stefano; Chiarucci, Michel; Fabrizi, Giancarlo; Goggiamani, Antonella; Ram�n, Rub�n S; Nolan, Steven P; Bandini, Marco
Chemoselectivity in Chemical Biology: Acyl Transfer Reactions with Sulfur and Selenium
CONSPECTUS A critical source of insight into biological function is derived from the chemist�s ability to create new covalent bonds between molecules, whether they are endogenous or exogenous to a biological system. A daunting impediment to selective bond formation, however, is the myriad of reactive functionalities present in biological milieu. The high reactivity of the most abundant molecule in biology�water�makes the challenges all the more difficult. We have met these challenges by exploiting the reactivity of sulfur and selenium in acyl transfer reactions. The reactivity of both sulfur and selenium is high compared to that of their chalcogen congener, oxygen. In this Account, we highlight recent developments in this arena, emphasizing contributions from our laboratory. One focus of our research is furthering the chemistry of native chemical ligation (NCL) and expressed protein ligation (EPL), two related processes that enable the synthesis and semisynthesis of proteins. These techniques exploit the lower pKa of thiols and selenols relative to alcohols. Although a deprotonated hydroxyl group in the side chain of a serine residue is exceedingly rare in a biological context, the pKa value of the thiol in cysteine (8.5) and of the selenol in selenocysteine (5.7) often render these side chains anionic under physiological conditions. NCL and EPL take advantage of the high nucleophilicity of the thiolate as well as its utility as a leaving group, and we have expanded the scope of these methods to include selenocysteine. Although the genetic code limits the components of natural proteins to 20 or so ?-amino acids, NCL and EPL enable the semisynthetic incorporation of a limitless variety of nonnatural modules into proteins. These modules are enabling chemical biologists to interrogate protein structure and function with unprecedented precision. We are also pursuing the further development of the traceless Staudinger ligation, through which a phosphinothioester and azide form an amide. We first reported this chemical ligation method, which leaves no residual atoms in the product, in 2000. Our progress in effecting the reaction in water, without an organic co-solvent, was an important step in the expansion of its utility. Moreover, we have developed the traceless Staudinger reaction as a means for immobilizing proteins on a solid support, providing a general method of fabricating microarrays that display proteins in a uniform orientation. Along with NCL and EPL, the traceless Staudinger ligation has made proteins more readily accessible targets for chemical synthesis and semisynthesis. The underlying acyl transfer reactions with sulfur and selenium provide an efficient means to synthesize, remodel, and immobilize proteins, and they have enabled us to interrogate biological systems.
McGrath, Nicholas A.; Raines, Ronald T.
Chemoselectivity in chemical biology: acyl transfer reactions with sulfur and selenium.
A critical source of insight into biological function is derived from the chemist's ability to create new covalent bonds between molecules, whether they are endogenous or exogenous to a biological system. A daunting impediment to selective bond formation, however, is the myriad of reactive functionalities present in biological milieu. The high reactivity of the most abundant molecule in biology, water, makes the challenges all the more difficult. We have met these challenges by exploiting the reactivity of sulfur and selenium in acyl transfer reactions. The reactivity of both sulfur and selenium is high compared with that of their chalcogen congener, oxygen. In this Account, we highlight recent developments in this arena, emphasizing contributions from our laboratory. One focus of our research is furthering the chemistry of native chemical ligation (NCL) and expressed protein ligation (EPL), two related processes that enable the synthesis and semisynthesis of proteins. These techniques exploit the lower pK(a) of thiols and selenols relative to alcohols. Although a deprotonated hydroxyl group in the side chain of a serine residue is exceedingly rare in a biological context, the pK(a) values of the thiol in cysteine (8.5) and of the selenol in selenocysteine (5.7) often render these side chains anionic under physiological conditions. NCL and EPL take advantage of the high nucleophilicity of the thiolate as well as its utility as a leaving group, and we have expanded the scope of these methods to include selenocysteine. Although the genetic code limits the components of natural proteins to 20 or so ?-amino acids, NCL and EPL enable the semisynthetic incorporation of a limitless variety of nonnatural modules into proteins. These modules are enabling chemical biologists to interrogate protein structure and function with unprecedented precision. We are also pursuing the further development of the traceless Staudinger ligation, through which a phosphinothioester and azide form an amide. We first reported this chemical ligation method, which leaves no residual atoms in the product, in 2000. Our progress in effecting the reaction in water, without an organic cosolvent, was an important step in the expansion of its utility. Moreover, we have developed the traceless Staudinger reaction as a means for immobilizing proteins on a solid support, providing a general method of fabricating microarrays that display proteins in a uniform orientation. Along with NCL and EPL, the traceless Staudinger ligation has made proteins more readily accessible targets for chemical synthesis and semisynthesis. The underlying acyl transfer reactions with sulfur and selenium provide an efficient means to synthesize, remodel, and immobilize proteins, and they have enabled us to interrogate biological systems. PMID:21639109
McGrath, Nicholas A; Raines, Ronald T
Multi-Component One-pot Synthesis of the Tumor-Associated Carbohydrate Antigen Globo-H Based on Pre-activation of Thioglycosyl Donors
Two efficient routes for rapid assembly of the tumor-associated carbohydrate antigen Globo-H hexasaccharide 2 by the pre-activation based iterative one pot strategy are reported. The first method involves the sequential coupling of four glycosyl building blocks, leading to the desired hexasaccharide in 47% overall yield in one-pot. Although model study on constructing the challenging Gal-?-1,4-Gal linkage in Gb3 trisaccharide yielded the desired ? linkage almost exclusively, similar approach to assemble the hexasaccharide led to formation of significant amount of ? anomer. As an alternative, the second synthesis utilizes three components in one pot with the Gal-?-1,4-Gal linkage pre-formed, producing the desired hexasaccharide in a similar overall yield as the four component approach. Both methods demonstrate that oligosaccharides containing ? and ? linkages within the same molecule can be constructed in one pot via the pre-activation based approach with higher glyco-assembly efficiencies than the automated solid phase synthesis strategy. Furthermore, because glycosylations can be carried out independent of anomeric reactivities of donors, it is not necessary to differentiate anomeric reactivities of building blocks through extensive protective group adjustment for chemoselective glycosylation. This confers great flexibilities in building block design allowing matching of the donor with the acceptor leading to improved overall yield.
Tailor Made Synthesis of T-Shaped and ?-STACKED Dimers in the Gas Phase: Concept for Efficient Drug Design and Material Synthesis
Non-covalent interactions play a key role in governing the specific functional structures of biomolecules as well as materials. Thus molecular level understanding of these intermolecular interactions can help in efficient drug design and material synthesis. It has been found from X-ray crystallography that pure hydrocarbon solids (i.e. benzene, hexaflurobenzene) have mostly slanted T-shaped (herringbone) packing arrangement whereas mixed solid hydrocarbon crystals (i.e. solid formed from mixtures of benzene and hexafluorobenzene) exhibit preferentially parallel displaced (PD) ?-stacked arrangement. Gas phase spectroscopy of the dimeric complexes of the building blocks of solid pure benzene and mixed benzene-hexafluorobenzene adducts exhibit similar structural motifs observed in the corresponding crystal strcutures. In this talk, I will discuss about the jet-cooled dimeric complexes of indole with hexafluorobenzene and p-xylene in the gas phase using Resonant two photon ionzation and IR-UV double resonance spectroscopy combined with quantum chemistry calculations. In stead of studying benzene...p-xylene and benzene...hexafluorobenzene dimers, we have studied corresponding indole complexes because N-H group is much more sensitive IR probe compared to C-H group. We have observed that indole...hexafluorobenzene dimer has parallel displaced (PD) ?-stacked structure whereas indole...p-xylene has slanted T-shaped structure. We have shown here selective switching of dimeric structure from T-shaped to ?-stacked by changing the substituent from electron donating (-CH3) to electron withdrawing group (fluorine) in one of the complexing partners. Thus, our results demonstrate that efficient engineering of the non-covalent interactions can lead to efficient drug design and material synthesis.
Kumar, Sumit; Das, Aloke
The application of vinylogous iminium salt derivatives to an efficient relay synthesis of the pyrrole containing alkaloids polycitone A and B
A new and efficient relay synthesis of the marine natural products polycitone A and B is described. The new strategy relies on the formation of 2,4-disubstituted pyrroles from a vinamidinium salt followed by electrophilic substitution at the 5-position of the pyrrole and Suzuki coupling at the 4-position to produce the tetrasubstituted heterocycle efficiently and with complete control of regiochemistry.
John T. Gupton; Robert B. Miller; Keith E. Krumpe; Stuart C. Clough; Edith J. Banner; Rene P. F. Kanters; Karen X. Du; Kartik M. Keertikar; Nicholas E. Lauerman; John M. Solano; Bret R. Adams; Daniel W. Callahan; Barrett A. Little; Austin B. Scharf; James A. Sikorski
Novel and efficient one-pot five- and six-component reactions for the stereoselective synthesis of highly functionalized enaminones and dithiocarbamates.
Efficient methods for stereoselective synthesis of polyfunctional (E)-enaminones and (Z)-dithiocarbamates via one-pot five- and six-component sequential Ugi/Nucleophilic addition reactions are described. High yields and high bond forming efficiency, and simple operations are the advantages of this method. PMID:21072590
Bararjanian, Morteza; Balalaie, Saeed; Rominger, Frank; Movassagh, Barahman; Bijanzadeh, Hamid Reza
Gold nanoparticles supported on titanium dioxide: an efficient catalyst for highly selective synthesis of benzoxazoles and benzimidazoles.
A highly efficient and selective reaction for the synthesis of 2-substituted benzoxazoles and benzimidazoles catalyzed by Au/TiO2 has been developed via two hydrogen-transfer processes. This reaction has a good tolerance to air and water, a wide substrate scope, and represents a new avenue for practical C-N and C-O bond formation. More importantly, no additional additives, oxidants and reductants are required for the reaction and the catalyst can be recovered and reused readily. PMID:24776805
Tang, Lin; Guo, Xuefeng; Yang, Yu; Zha, Zhenggen; Wang, Zhiyong
A facile and efficient ultrasound-assisted synthesis of novel dispiroheterocycles through 1,3-dipolar cycloaddition reactions.
A facile and efficient one-pot three-component procedure for synthesis of novel dispirooxindolecyclo[pyrrolo[1,2-c]thiazole-6,5'-thiazolidine] derivatives without any catalysts under ultrasonic condition has been developed. Combining with the advantages of sonochemistry, such as mild reaction conditions, good yield and short reaction times, we have made a progress on construction of novel disiproheterocyclic compounds via the 1,3-dipolar cycloaddition of azomethine ylides. Several experiments were especially carried out for investigating the acceleration mechanism of ultrasound on the cycloaddition. PMID:21855389
Hu, Yu; Zou, Yi; Wu, Hui; Shi, Daqing
Efficient Microwave-assisted One-pot Three-component Synthesis of 2,3-Disubstituted Benzofurans under Sonogashira Conditions
An efficient one-pot method for the synthesis of 2,3-disubstituted benzo[b]furans from commercially available 2-iodophenols, terminal acetylenes and aryl iodides has been developed utilizing Sonogashira reaction conditions. After an initial Sonogashira coupling of the 2-iodophenol with the terminal alkyne, cyclization involving the aryl iodide provides the 2,3-disubstituted benzo[b]furan in good to excellent yields. The use of microwave irradiation shortens the reaction times and minimizes the side products. This methodology is especially useful for the construction of libraries of highly substituted benzo[b]furans and their analogues.
Markina, Nataliya A.; Chen, Yu; Larock, Richard C.
An organocatalytic highly efficient approach to the direct synthesis of substituted carbazoles in water.
A simple, mild, green, catalytic and general procedure for the direct synthesis of highly functionalized 1-methoxycarbonyl-2-aryl/alkyl-3-nitro-9H-carbazoles has been achieved in water medium via a one-pot domino Michael-Henry/aromatization reaction of methyl 2-(3-formyl-1H-indol-2-yl)acetates with aryl/alky-substituted ?-nitroolefins under air using DABCO (30 mol%) as an organocatalyst. In addition, the bench scale synthesis can be performed without using toxic organic solvents and a biologically important new fused carbazole has been prepared. PMID:24189837
Jaiswal, Pradeep Kumar; Biswas, Soumen; Singh, Shivendra; Samanta, Sampak
Prins-Type Macrocyclizations as an Efficient Ring-Closing Strategy in Natural Product Synthesis
Prins-type macrocyclizations have recently emerged as a successful strategy in the synthesis of polyketide-derived natural products. This reaction provides a concise and selective means to form tetrahydropyran-containing macrocyclic rings of varying size. A high degree of functionality within the macrocycle is tolerated and the yields for these transformations are typically good to excellent. Since the initial report of a Prins macrocyclization reaction in 1979, examples of this approach did not re-emerge until 2008. However, the use of this method in natural product synthesis has rapidly gained momentum in the synthetic community, with multiple examples of this macrocyclization tactic reported in the recent literature.
Crane, Erika A.; Scheidt, Karl A.
Chemoselective Nitro Group Reduction and Reductive Dechlorination Initiate Degradation of 2-Chloro-5-Nitrophenol by Ralstonia eutropha JMP134
Ralstonia eutropha JMP134 utilizes 2-chloro-5-nitrophenol as a sole source of nitrogen, carbon, and energy. The initial steps for degradation of 2-chloro-5-nitrophenol are analogous to those of 3-nitrophenol degradation in R. eutropha JMP134. 2-Chloro-5-nitrophenol is initially reduced to 2-chloro-5-hydroxylaminophenol, which is subject to an enzymatic Bamberger rearrangement yielding 2-amino-5-chlorohydroquinone. The chlorine of 2-amino-5-chlorohydroquinone is removed by a reductive mechanism, and aminohydroquinone is formed. 2-Chloro-5-nitrophenol and 3-nitrophenol induce the expression of 3-nitrophenol nitroreductase, of 3-hydroxylaminophenol mutase, and of the dechlorinating activity. 3-Nitrophenol nitroreductase catalyzes chemoselective reduction of aromatic nitro groups to hydroxylamino groups in the presence of NADPH. 3-Nitrophenol nitroreductase is active with a variety of mono-, di-, and trinitroaromatic compounds, demonstrating a relaxed substrate specificity of the enzyme. Nitrosobenzene serves as a substrate for the enzyme and is converted faster than nitrobenzene.
Schenzle, Andreas; Lenke, Hiltrud; Spain, Jim C.; Knackmuss, Hans-Joachim
Chemoselective nitro group reduction and reductive dechlorination initiate degradation of 2-chloro-5-nitrophenol by Ralstonia eutropha JMP134
Ralstonia eutropha JMP134 utilizes 2-chloro-5-nitrophenol as a sole source of nitrogen, carbon, and energy. The initial steps for degradation of 2-chloro-5-nitrophenol are analogous to those of 3-nitrophenol degradation in R. eutropha JMP134, 2-chloro-5-nitrophenol is initially reduced to 2-chloro-5-hydroxylaminophenol, which is subject to an enzymatic Bamberger rearrangement yielding 2-amino-5-chlorohydroquinone. The chlorine of 2-amino-5-chlorohydroquinone is removed by a reductive mechanism, and aminohydroquinone is formed. 2-Chloro-5-nitrophenol and 3-nitrophenol induce the expression of 3-nitrophenol nitroreductase, of 3-hydroxylaminophenol mutase, and of the dechlorinating activity. 3-Nitrophenol nitroreductase catalyzes chemoselective reduction of aromatic nitro groups to hydroxylamino groups in the presence of NADPH. 3-Nitrophenol nitroreductase is active with a variety of mono-, di-, and trinitroaromatic compounds, demonstrating a relaxed substrate specificity of the enzyme. Nitrosobenzene serves as a substrate for the enzyme and is converted faster than nitrobenzene.
Schenzle, A.; Lenke, H.; Knackmuss, H.J. [Univ. Stuttgart (Germany); Spain, J.C. [AFRL/MRLQ, Tyndall AFB, FL (United States). Armstrong Lab.
Rapid and efficient synthesis of soluble graphene nanosheets using N-methyl-p-aminophenol sulfate as a reducing agent.
Mass production of soluble graphene still remains a challenge, although several methodologies have been proposed. Here we report a rapid and efficient method for the synthesis of soluble graphene nanosheets (GNSs) with long-term dispersion stability in both aqueous and common organic solvents. Within only 12 min at 95 �C, exfoliated graphite oxide in ammonia solution (pH 10) was reduced to soluble GNSs using N-methyl-p-aminophenol sulfate (metol) as a reducing agent without external stabilizers. The prepared GNSs were characterized by different techniques and a comparison of metol and hydrazine hydrate as reducing agents was made. The results indicated that, with the advantages of being rapid, efficient, inexpensive and relatively environmentally friendly, the reduction of graphite oxide into soluble GNSs by metol is a promising substitute for hydrazine hydrate in the mass production of soluble GNSs. PMID:23128046
Wang, Xialie; Wen, Xiaohong; Liu, Zhanpeng; Tan, Yi; Yuan, Ye; Zhang, Ping
Efficient and systematic synthesis of a small glycoconjugate library having human complex type oligosaccharides
To prepare a small library of homogeneous glycoconjugates with varying oligosaccharide structures, a combinatorial strategy was employed. The target glycopeptide was divided into two peptide segments (A and B) and both were prepared by solid phase peptide synthesis. These peptides, which can be coupled by native chemical ligation through an amide bond, were subsequently coupled to two kinds of human
Takefumi Murase; Takashi Tsuji; Yasuhiro Kajihara
Efficient Synthesis of ?-Lactams by a Tandem Reductive Amination/Lactamization Sequence
A three-component method for synthesizing highly-substituted ?-lactams from readily available maleimides, aldehydes and amines is described. A new reductive amination/intramolecular lactamization sequence provides a straightforward route to the lactam products in a single manipulation. The general utility of this method is demonstrated by the parallel synthesis of a ?-lactam library.
Noth, Julica; Frankowski, Kevin J.; Neuenswander, Benjamin; Aube, Jeffrey; Reiser, Oliver
Rapid microwave synthesis of indium filled skutterudites: An energy efficient route to high performance thermoelectric materials
Graphical abstract: Filled skutterudites are promising thermoelectric materials. We report the microwave assisted synthesis of CoSb{sub 3} and In{sub 0.2}Co{sub 4}Sb{sub 12}. This method reduces the calcination time for skutterudite phase formation from 2 days to 2 min, thereby significantly reducing the time and energy needed to produce materials suitable for property and device testing. Highlights: Black-Right-Pointing-Pointer The microwave assisted solid state synthesis of CoSb{sub 3} and In{sub 0.2}Co{sub 4}Sb{sub 12} is reported. Black-Right-Pointing-Pointer This method allows the calcination time to be reduced from 2 days to 2 min. Black-Right-Pointing-Pointer Physical properties of microwave samples match those prepared conventionally. -- Abstract: Filled skutterudites are promising thermoelectric materials due to reduced thermal conductivity upon inserting a guest atom or 'rattler' into the CoSb{sub 3} structure. By using an indium rattler dimensionless Figure of Merit (ZT) values >1 at 650 K have been reported. The conventional synthesis of these compounds typically takes several days ({approx}3 days) to obtain the final well-sintered material for property measurements. We report here a microwave-assisted synthesis method that reduces the initial calcination time from 2 days to 2 min. This route significantly reduces the time needed to produce materials suitable for property and device testing.
Biswas, Krishnendu, E-mail: firstname.lastname@example.com [Department of Chemistry, Oregon State University, Corvallis, OR 97331 (United States)] [Department of Chemistry, Oregon State University, Corvallis, OR 97331 (United States); Muir, Sean, E-mail: email@example.com [Department of Chemistry, Oregon State University, Corvallis, OR 97331 (United States)] [Department of Chemistry, Oregon State University, Corvallis, OR 97331 (United States); Subramanian, M.A., E-mail: email@example.com [Department of Chemistry, Oregon State University, Corvallis, OR 97331 (United States)
Efficient room-temperature synthesis of a highly strained carbon nanohoop fragment of buckminsterfullerene
Warped carbon-rich molecules have captured the imagination of scientists across many disciplines. Owing to their promising materials properties and challenging synthesis, strained hydrocarbons are attractive targets that push the limits of synthetic methods and molecular design. Herein we report the synthesis and characterization of [5]cycloparaphenylene ([5]CPP), a carbon nanohoop that can be envisaged as an open tubular fragment of C60, the equator of C70 fullerene and the unit cycle of a [5,5] armchair carbon nanotube. Given its calculated 119�kcal�mol?1 strain energy and severely distorted benzene rings, this synthesis, which employs a room-temperature macrocyclization of a diboronate precursor, single-electron reduction and elimination, is remarkably mild and high yielding (27% over three steps). Single-crystal X-ray diffraction data were obtained to confirm its geometry and previously disputed benzenoid character. First and second pseudoreversible oxidation and reduction events were observed via cyclic voltammetry. The ease of synthesis, high solubility and narrowest optical HOMO/LUMO gap of any para-polyphenylene synthesized make [5]CPP a desirable new material for organic electronics.
Evans, Paul J.; Darzi, Evan R.; Jasti, Ramesh
Air- and moisture-stable amphoteric molecules: enabling reagents in synthesis.
Researchers continue to develop chemoselective synthesis strategies with the goal of rapidly assembling complex molecules. As one appealing approach, chemists are searching for new building blocks that include multiple functional groups with orthogonal chemical reactivity. Amphoteric molecules that possess nucleophilic and electrophilic sites offer a versatile platform for the development of chemoselective transformations. As part of a program focused on new methods of synthesis, we have been developing this type of reagents. This Account highlights examples of amphoteric molecules developed by our lab since 2006. We have prepared and evaluated aziridine aldehydes, a class of stable unprotected ?-amino aldehydes. Structurally, aziridine aldehydes include both a nucleophilic amine nitrogen and an electrophilic aldehyde carbon over the span of three atoms. Under ambient conditions, these compounds exist as homochiral dimers with an aziridine-fused five-membered cyclic hemiaminal structure. We have investigated chemoselective reactions of aziridine aldehydes that involve both the aziridine and aldehyde functionalities. These transformations have produced a variety of densely functionalized nitrogen-containing compounds, including amino aldehydes, 1,2-diamines, reduced hydantoins, C-vinyl or alkynyl aziridines, and macrocyclic peptides. We have also developed air- and moisture-stable ?-boryl aldehydes, another class of molecules that are kinetically amphoteric. The ?-boryl aldehydes contain a tetracoordinated N-methyliminodiacetyl (MIDA) boryl substituent, which stabilizes the ?-metalloid carbonyl system and prevents isomerization to its O-bond enolate form. Primarily taking advantage of chemoselective transformations at the aldehyde functionality, these ?-boryl aldehydes have allowed us to synthesize a series of new functionalized boron-containing compounds that are difficult or impossible to prepare using established protocols, such as ?-borylcarboxylic acids, boryl alcohols, enol ethers, and enamides. Using ?-borylcarboxylic acids as starting materials, we have also prepared several new amphoteric borylated reagents, such as ?-boryl isocyanates, isocyanides, and acylboronates. These compounds are versatile building blocks in their own right, enabling the rapid synthesis of other boron-containing molecules. PMID:24495255
He, Zhi; Zajdlik, Adam; Yudin, Andrei K
Retention of OsNMD3 in the cytoplasm disturbs protein synthesis efficiency and affects plant development in rice.
The ribosome is the basic machinery for translation, and biogenesis of ribosomes involves many coordinated events. However, knowledge about ribosomal dynamics in higher plants is very limited. This study chose a highly conserved trans-factor, the 60S ribosomal subunit nuclear export adaptor NMD3, to characterize the mechanism of ribosome biogenesis in the monocot plant Oryza sativa (rice). O. sativa NMD3 (OsNMD3) shares all the common motifs and shuttles between the nucleus and cytoplasm via CRM1/XPO1. A dominant negative form of OsNMD3 with a truncated nuclear localization sequence (OsNMD3(?NLS)) was retained in the cytoplasm, consequently interfering with the release of OsNMD3 from pre-60S particles and disturbing the assembly of ribosome subunits. Analyses of the transactivation activity and cellulose biosynthesis level revealed low protein synthesis efficiency in the transgenic plants compared with the wild-type plants. Pharmaceutical treatments demonstrated structural alterations in ribosomes in the transgenic plants. Moreover, global expression profiles of the wild-type and transgenic plants were investigated using the Illumina RNA sequencing approach. These expression profiles suggested that overexpression of OsNMD3(?NLS) affected ribosome biogenesis and certain basic pathways, leading to pleiotropic abnormalities in plant growth. Taken together, these results strongly suggest that OsNMD3 is important for ribosome assembly and the maintenance of normal protein synthesis efficiency. PMID:24723395
Shi, Yanyun; Liu, Xiangling; Li, Rui; Gao, Yaping; Xu, Zuopeng; Zhang, Baocai; Zhou, Yihua
Retention of OsNMD3 in the cytoplasm disturbs protein synthesis efficiency and affects plant development in rice
The ribosome is the basic machinery for translation, and biogenesis of ribosomes involves many coordinated events. However, knowledge about ribosomal dynamics in higher plants is very limited. This study chose a highly conserved trans-factor, the 60S ribosomal subunit nuclear export adaptor NMD3, to characterize the mechanism of ribosome biogenesis in the monocot plant Oryza sativa (rice). O. sativa NMD3 (OsNMD3) shares all the common motifs and shuttles between the nucleus and cytoplasm via CRM1/XPO1. A dominant negative form of OsNMD3 with a truncated nuclear localization sequence (OsNMD3?NLS) was retained in the cytoplasm, consequently interfering with the release of OsNMD3 from pre-60S particles and disturbing the assembly of ribosome subunits. Analyses of the transactivation activity and cellulose biosynthesis level revealed low protein synthesis efficiency in the transgenic plants compared with the wild-type plants. Pharmaceutical treatments demonstrated structural alterations in ribosomes in the transgenic plants. Moreover, global expression profiles of the wild-type and transgenic plants were investigated using the Illumina RNA sequencing approach. These expression profiles suggested that overexpression of OsNMD3?NLS affected ribosome biogenesis and certain basic pathways, leading to pleiotropic abnormalities in plant growth. Taken together, these results strongly suggest that OsNMD3 is important for ribosome assembly and the maintenance of normal protein synthesis efficiency.
Applied reaction dynamics: efficient synthesis gas production via single collision partial oxidation of methane to CO on Rh111.
Supersonic molecular beams have been used to determine the yield of CO from the partial oxidation of CH4 on a Rh111 catalytic substrate, CH4+12O2-->CO+2H2, as a function of beam kinetic energy. These experiments were done under ultrahigh vacuum conditions with concurrent molecular beams of O2 and CH4, ensuring that there was only a single collision for the CH4 to react with the surface. The fraction of CH4 converted is strongly dependent on the normal component of the incident beam's translational energy, and approaches unity for energies greater than approximately 1.3 eV. Comparison with a simplified model of the methane-Rh111 reactive potential gives insight into the barrier for methane dissociation. These results demonstrate the efficient conversion of methane to synthesis gas, CO+2H2, are of interest in hydrogen generation, and have the optimal stoichiometry for subsequent utilization in synthetic fuel production (Fischer-Tropsch or methanol synthesis). Moreover, under the reaction conditions explored, no CO2 was detected, i.e., the reaction proceeded with the production of very little, if any, unwanted greenhouse gas by-products. These findings demonstrate the efficacy of overcoming the limitations of purely thermal reaction mechanisms by coupling nonthermal mechanistic steps, leading to efficient C-H bond activation with subsequent thermal heterogeneous reactions. PMID:17029475
Gibson, K D; Viste, M; Sibener, S J
Applied reaction dynamics: Efficient synthesis gas production via single collision partial oxidation of methane to CO on Rh(111)
Supersonic molecular beams have been used to determine the yield of CO from the partial oxidation of CH4 on a Rh(111) catalytic substrate, CH4+(1/2)O2-->CO+2H2, as a function of beam kinetic energy. These experiments were done under ultrahigh vacuum conditions with concurrent molecular beams of O2 and CH4, ensuring that there was only a single collision for the CH4 to react with the surface. The fraction of CH4 converted is strongly dependent on the normal component of the incident beam's translational energy, and approaches unity for energies greater than ~1.3 eV. Comparison with a simplified model of the methane-Rh(111) reactive potential gives insight into the barrier for methane dissociation. These results demonstrate the efficient conversion of methane to synthesis gas, CO+2H2, are of interest in hydrogen generation, and have the optimal stoichiometry for subsequent utilization in synthetic fuel production (Fischer-Tropsch or methanol synthesis). Moreover, under the reaction conditions explored, no CO2 was detected, i.e., the reaction proceeded with the production of very little, if any, unwanted greenhouse gas by-products. These findings demonstrate the efficacy of overcoming the limitations of purely thermal reaction mechanisms by coupling nonthermal mechanistic steps, leading to efficient C-H bond activation with subsequent thermal heterogeneous reactions.
Gibson, K. D.; Viste, M.; Sibener, S. J.
One-Pot Synthesis of 2,4,5Trisubstituted Imidazoles Using MoO3\\/SiO2, an Efficient and Recyclable Catalyst
A simple one-pot synthesis has been developed for the synthesis of 2,4,5-trisubstituted imidazoles using an efficient and recyclable MoO3\\/SiO2 solid acid catalyst by condensation of benzil or benzoin, benzaldehyde, and ammonium acetate in acetonitrile as a solvent. Using this solid catalyst, the reactions could be carried out under mild reaction conditions with very good yield of imidazoles, up to 95%.
Sidhanath V. Bhosale; Mohan B. Kalyankar; Santosh V. Nalage; Dattatry S. Bhosale; Swati L. Pandhare; Trupti V. Kotbagi; Shubhangi B. Umbarkar; Mohan K. Dongare
Ultrasound-assisted one-pot synthesis of substituted coumarins catalyzed by poly(4-vinylpyridinium) hydrogen sulfate as an efficient and reusable solid acid catalyst.
Poly(4-vinylpyridinium) hydrogen sulfate solid acid was found to be efficient catalyst for synthesis of substituted coumarins via Pechmann reaction using ultrasound irradiation at room temperature and neat condition in high yields with short reaction times. This methodology offers momentous improvements over various options for the synthesis of coumarins with regard to yield of products, simplicity in operation and green aspects by avoiding toxic catalysts and solvents. Further, the catalyst can be reused and recovered for several times. PMID:23395258
Khaligh, Nader Ghaffari
Rapid and efficient ultrasound-assisted method for the combinatorial synthesis of spiro[indoline-3,4'-pyrano[2,3-c]pyrazole] derivatives.
An efficient one-pot synthesis of spiro[indoline-3,4'-pyrano[2,3-c]pyrazole] derivatives by four-component reaction of hydrazine, ?-keto ester, isatin, and malononitrile or ethyl cyanoacetate catalyzed by piperidine under ultrasound irradiation is described. This synthesis was confirmed to follow the group-assistant-purification chemistry (GAP) chemistry process, which can avoid traditional chromatography and recrystallization purifications. PMID:22141731
Zou, Yi; Hu, Yu; Liu, Hai; Shi, Daqing
Ammonia treatment of wheat straw. 2. Efficiency of microbial protein synthesis, rumen microbial protein pool size and turnover, and small intestinal protein digestion in sheep
Ammonia-treated wheat straw (AWS) was compared with untreated wheat straw (UWS) and untreated wheat straw supplemented with urea (SWS) in an experiment with 6 wether sheep. Microbial protein synthesis increased after ammonia treatment due to the higher intake of rumen degradable organic matter (OM). The efficiency of microbial protein synthesis was low for all diets, averaging 22.1 g N\\/kg apparently
S. J. Oosting; T. C. Viets; S. C. W. Lammers-Wienhoven; Bruchem van J
Synthesis of human growth hormone-releasing hormone via three-fragment serine/threonine ligation (STL).
The synthesis of human growth hormone-releasing hormone (hGH-RH), by the chemoselective serine/threonine ligations (STLs) of three unprotected peptide fragments, is reported. To allow for the multiple-fragment ligation, we chose the Msz (p-(methylsulfinyl)benzyloxycarbonyl) group, which is compatible with the preparation of peptide salicylaldehyde esters via Fmoc-SPPS and readily removed by reductive acidolysis, to protect the serine and threonine residue at the N-terminus. PMID:23884451
Zhang, Yinfeng; Li, Tianlu; Li, Xuechen
Sequence and structure-specific elements of HERG mRNA determine channel synthesis and trafficking efficiency.
Human ether-�-gogo-related gene (HERG) encodes a potassium channel that is highly susceptible to deleterious mutations resulting in susceptibility to fatal cardiac arrhythmias. Most mutations adversely affect HERG channel assembly and trafficking. Why the channel is so vulnerable to missense mutations is not well understood. Since nothing is known of how mRNA structural elements factor in channel processing, we synthesized a codon-modified HERG cDNA (HERG-CM) where the codons were synonymously changed to reduce GC content, secondary structure, and rare codon usage. HERG-CM produced typical IKr-like currents; however, channel synthesis and processing were markedly different. Translation efficiency was reduced for HERG-CM, as determined by heterologous expression, in vitro translation, and polysomal profiling. Trafficking efficiency to the cell surface was greatly enhanced, as assayed by immunofluorescence, subcellular fractionation, and surface labeling. Chimeras of HERG-NT/CM indicated that trafficking efficiency was largely dependent on 5' sequences, while translation efficiency involved multiple areas. These results suggest that HERG translation and trafficking rates are independently governed by noncoding information in various regions of the mRNA molecule. Noncoding information embedded within the mRNA may play a role in the pathogenesis of hereditary arrhythmia syndromes and could provide an avenue for targeted therapeutics. PMID:23608144
Sroubek, Jakub; Krishnan, Yamini; McDonald, Thomas V
Green synthesis of polysaccharide/gold nanoparticle nanocomposite: an efficient ammonia sensor.
A low cost eco-friendly method for the synthesis of gold nanoparticles (AuNPs) using guar gum (GG) as a reducing agent is reported. The nanoparticles obtained are characterized by UV-vis spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X-ray diffraction (XRD). Based on these results, a potential mechanism for this method of AuNPs synthesis is discussed. GG/AuNPs nanocomposite (GG/AuNPs NC) was exploited for optical sensor for detection of aqueous ammonia based on surface plasmon resonance (SPR). It was found to have good reproducibility, response times of ?10 s and excellent sensitivity with a detection limit of 1ppb (parts-per-billion). This system allows the rapid production of an ultra-low-cost GG/AuNPs NC-based aqueous ammonia sensor. PMID:23544533
Pandey, Sadanand; Goswami, Gopal K; Nanda, Karuna K
Highly efficient automated synthesis of [(11)C]choline for multi dose utilization.
[(11)C]Choline has been under investigation as a PET ligand for imaging tumor tissue, especially prostate cancer. An improved, automated synthesis of the tracer now was established. [(11)C] Choline was produced by labeling 2-(dimethylamino)-ethanol (DMAE) with [(11)C]CH(3)I in a Tefzel tube at room temperature without solvent. The product was purified using a cation exchange cartridge. Reaction conditions were optimized with respect to synthesis time and amount of DMAE, resulting in radiochemical yields higher than 80% using 60 microl of DMAE in 20 min, radiochemical purity was >99% and residual DMAE was below 10 ppm. After (11)C-production of 1h at 50 microA [(11)C]choline activities of 30.0+/-5.6 GBq (n = 29) were obtained in sterile solution ready for intravenous administration. PMID:15110347
Reischl, G; Bieg, C; Schmiedl, O; Solbach, C; Machulla, H-J
Peptide dendrimers as efficient and biocompatible gene delivery vectors: Synthesis and in vitro characterization
We report the synthesis and characterization of different generations of dendritic poly(l-lysine) vectors, and their use for in vitro gene transfection. Gel retardation assay revealed that the dendrimers could form complexes with plasmid DNAs (pDNAs), evident from the inhibition of the migration of pDNA at the N\\/P ratios of 0.5, 1 and 2 by G3, G4 and G5 dendritic generations,
Kui Luo; Caixia Li; Gang Wang; Yu Nie; Bin He; Yao Wu; Zhongwei Gu
Efficient synthesis of substituted piperazinones via tandem reductive amination�cyclization
A new strategy for the preparation of substituted piperazinones features a tandem reductive coupling and SN2-cyclization of a 2-chloro-N-(2-oxoalkyl)acetamide (1) and a primary amine (2). The method is convenient for diversity-oriented synthesis, since a wide variety of amines may be used in the ring-forming reaction to produce N-substituted piperazinones (3).
Christopher J. Dinsmore; C. Blair Zartman
An Efficient Synthesis of (?)-Grandisol Featuring 1,5-Enyne Metathesis
An eight step synthesis of (�)-grandisol features a key sequence involving a high-yielding, microwave-assisted enyne metathesis to yield a 1-alkenylcyclobutene that is semihydrogenated to yield a silyl-protected grandisol. Metathesis catalyst screens revealed an intriguing trend whereby substrate conversion correlated strongly with the identity of the ligands on the catalyst. In addition, new reactivity of 1-alkenylcyclobutenes toward hydrogenation is described.
Graham, Thomas J. A.; Gray, Erin E.; Burgess, James M.; Goess, Brian C.
An Efficient List-Based Scheduling Algorithm for High-Level Synthesis
Scheduling is considered as the most important task in high-level synthesis process. This paper presents a novel list-based scheduling algorithm based on incorporating some information extracted from data flow graph (DFG) structure to guide the scheduler to find near-optimal\\/optimal schedules quickly. We have developed a novel approach based on DFG analysis that is totally done as preparation phase. This DFG
Azeddien M. Sllame; Vladim�r Dr�bek
An Efficient, Microwave-Assisted, One-Pot Synthesis of Indoles Under Sonogashira Conditions
A microwave-assisted, one-pot, three-component coupling reaction for the synthesis of indoles has been developed. The reaction is carried out in two steps under standard Sonogashira coupling conditions from an N-substituted/N,N-disubstituted 2-iodoaniline and a terminal alkyne, followed by the addition of acetonitrile and an aryl iodide. A variety of polysubstituted indoles have been prepared in moderate to excellent yields using the present method.
Chen, Yu; Markina, Nataliya A.; Larock, Richard C.
Efficient palladium-catalyzed double carbonylation of o-dibromobenzenes: synthesis of thalidomide.
We describe here a convenient and mild procedure for double carbonylation of o-dibromobenzenes with various 2-amino pyridines and naturally occurring amines, thus providing in good to excellent yields N-substituted phthalimides by using this palladium-catalyzed carbonylation procedure. Furthermore, for the first time we have applied the developed synthetic protocol for the synthesis of biologically active molecule thalidomide via a single step carbonylative cyclization reaction in excellent yield. PMID:24848729
Chen, Jianbin; Natte, Kishore; Spannenberg, Anke; Neumann, Helfried; Beller, Matthias; Wu, Xiao-Feng
Efficient Synthesis and Evaluation of Quorum Sensing Modulators Using Small Molecule Macroarrays
A method for the synthesis of small molecule macroarrays of N-acylated L-homoserine lactones (AHLs) is reported. A focused library of AHLs was constructed, and the macroarray platform was found to be compatible with both solution and agar-overlay assays using quorum-sensing (QS) reporter strains. Several QS antagonists were discovered and serve to showcase the macroarray as a straightforward technique for QS research.
Praneenararat, Thanit; Geske, Grant D.; Blackwell, Helen E.
A GP algorithm for efficient synthesis of GMC filters on a hexagonal FPAA structure
This work presents an approach based on Genetic Program- ming for the synthesis of continuous-time analog lters on a eld-programmable analog array. A multi-objective algo- rithm is used to synthesize both the topology and param- eter values of Gm-C lter structures to be instantiated on the FPAA based on a given lter specication. The pre- sented algorithm is highly adapted
Stanis Trendelenburg; Joachim Becker; Fabian Henrici; Yiannos Manoli
Silica: An efficient catalyst for one-pot regioselective synthesis of dithioethers
Summary The development of a silica-promoted highly selective synthesis of 1,2 or 1,3-dithioethers via solvent-free one-pot tandem reactions of an allyl bromide with excess thiol at room temperature is described. The choice of silica gel, either pre-calcined or moistened with water, exhibited notable regioselectivity in the formation of dithioethers. Plausible mechanistic routes were explored and postulated.
Kundu, Samir; Roy, Babli
Efficient synthesis of N-substituted-N'-arylcarbonylthioureas under solvent-free conditions
A convenient method for the synthesis of N-substituted-N'-arylcarbonylthioureas under solvent-free conditions has been developed. Ammonium thiocyanate and acid chlorides were mixed, and stirred at room temperature without a solvent, to give the corresponding isothiocyanates, which reacted smoothly with arylamines to produce the aryl(alkyl)carbonylthioureas in good yields. Unusually large values of JFH=12.2�15.1�Hz are observed for 1-(2-fluorobenzoyl)-thiourea derivatives, which provide information about
Issa Yavari; Mohammad Bagheri; Khalil Porshamsian; Safa Ali-Asgari
Simple enzymatic procedure for L-carnosine synthesis: whole-cell biocatalysis and efficient biocatalyst recycling.
?-Peptides and their derivates are usually stable to proteolysis and have an increased half-life compared with ?-peptides. Recently, ?-aminopeptidases were described as a new enzyme class that enabled the enzymatic degradation and formation of ?-peptides. As an alternative to the existing chemical synthesis routes, the aim of the present work was to develop a whole-cell biocatalyst for the synthesis and production of ?-peptides using this enzymatic activity. For the optimization of the reaction system we chose the commercially relevant ?,?-dipeptide L-carnosine (?-alanine-L-histidine) as model product. We were able to show that different recombinant yeast and bacteria strains, which overexpress a ?-peptidase, could be used directly as whole-cell biocatalysts for the synthesis of L-carnosine. By optimizing relevant reaction conditions for the best-performing recombinant Escherichia coli strain, such as pH and substrate concentrations, we obtained high l-carnosine yields of up to 71%. Long-time as well as biocatalyst recycling experiments indicated a high stability of the developed biocatalyst for at least five repeated batches. Application of the recombinant E. coli in a fed-batch process enabled the accumulation of l-carnosine to a concentration of 3.7 g l(-1). PMID:21255308
Heyland, Jan; Antweiler, Nicolai; Lutz, Jochen; Heck, Tobias; Geueke, Birgit; Kohler, Hans-Peter E; Blank, Lars M; Schmid, Andreas
Simple enzymatic procedure for l-carnosine synthesis: whole-cell biocatalysis and efficient biocatalyst recycling
Summary ??Peptides and their derivates are usually stable to proteolysis and have an increased half?life compared with ??peptides. Recently, ??aminopeptidases were described as a new enzyme class that enabled the enzymatic degradation and formation of ??peptides. As an alternative to the existing chemical synthesis routes, the aim of the present work was to develop a whole?cell biocatalyst for the synthesis and production of ??peptides using this enzymatic activity. For the optimization of the reaction system we chose the commercially relevant ?,??dipeptide l?carnosine (??alanine?l?histidine) as model product. We were able to show that different recombinant yeast and bacteria strains, which overexpress a ??peptidase, could be used directly as whole?cell biocatalysts for the synthesis of l?carnosine. By optimizing relevant reaction conditions for the best?performing recombinant Escherichia coli strain, such as pH and substrate concentrations, we obtained high l?carnosine yields of up to 71%. Long?time as well as biocatalyst recycling experiments indicated a high stability of the developed biocatalyst for at least five repeated batches. Application of the recombinant E. coli in a fed?batch process enabled the accumulation of l?carnosine to a concentration of 3.7?g?l?1.
Heyland, Jan; Antweiler, Nicolai; Lutz, Jochen; Heck, Tobias; Geueke, Birgit; Kohler, Hans-Peter E.; Blank, Lars M.; Schmid, Andreas
Templated synthesis of nickel nanoparticles: Toward heterostructured nanocomposites for efficient hydrogen storage
The world is currently facing an energy and environmental crisis for which new technologies are needed. Development of cost-competitive materials for catalysis and hydrogen storage on-board motor vehicles is crucial to lead subsequent generations into a more sustainable and energy independent future. This thesis presents work toward the scalable synthesis of bimetallic heterostructures that can enable hydrogen to compete with carbonaceous fuels by meeting the necessary gravimetric and volumetric energy densities and by enhancing hydrogen sorption/desorption kinetics near ambient temperatures and pressures. Utilizing the well-known phenomenon of hydrogen spillover, these bimetallic heterostructures could work by lowering the activation energy for hydrogenation and dehydrogenation of metals. Herein, we report a novel method for the scalable synthesis of silica templated zero-valent nickel particles (Ni?SiO2) that hold promise for the synthesis of nickel nanorods for use in bimetallic heterostructures for hydrogen storage. Our synthesis proceeds by chemical reduction of a nickel-hydrazine complex with sodium borohydride followed by calcination under hydrogen gas to yield silica encapsulated nickel particles. Transmission electron microscopy and powder X-ray diffraction were used to characterize the general morphology of the resultant nanocapsules as well as the crystalline phases of the incorporated Ni0 nanocrystals. The structures display strong magnetic behavior at room temperature and preliminary data suggests nickel particle size can be controlled by varying the amount of nickel precursor used in the synthesis. Calcination under different environments and TEM analysis provides evidence for an atomic migration mechanism of particle formation. Ni?SiO2 nanocapsules were used as seeds to induce heterogeneous nucleation and subsequent growth within the nanocapsule via electroless nickel plating. Nickel nanoparticle growth occurs under high temperature alkaline conditions, however silica nanocapsule integrity is not maintained due to the incompatibility of silica with the growth conditions. Silica nanocapsule integrity is maintained under low temperature neutral conditions, but nickel particle growth is not observed. Through FTIR and UV/Vis analysis, we show the degree of crosslinking and condensation increases in calcined silica compared to as-synthesized silica. We propose the increased density of the silica nanocapsule hinders mass transfer of the bulky nickel precursor complex from solution and onto the surface of the "catalytic" zero-valent nickel seed within the nanocapsule cavity. Decreasing the density of the silica nanocapsule can be achieved through co-condensation of tetraethylorthosilicate with an alkyl functionalized silane followed by calcination to remove the organic component or by chemical etching in alkaline solution, but will not be addressed in this thesis.
Nelson, Nicholas Cole
Remarkable effect of 2,2'-bipyridyl: mild and highly chemoselective deprotection of methoxymethyl (MOM) ethers in combination with TMSOTf (TESOTf)-2,2'-bipyridyl.
The remarkable effect of 2,2'-bipyridyl led to the successful development of the mild and highly chemoselective deprotection method of methoxymethyl (MOM) ethers using the combination of TMSOTf (or TESOTf) and 2,2'-bipyridyl; this method can be applied to the direct conversion of the MOM group to other ethereal protective groups (e.g. benzyloxymethyl) with the corresponding alcohols. PMID:19597615
Fujioka, Hiromichi; Kubo, Ozora; Senami, Kento; Minamitsuji, Yutaka; Maegawa, Tomohiro
Efficient Utilization of Greenhouse Gases in a Gas-to-Liquids Process Combined with CO2/Steam-Mixed Reforming and Fe-Based Fischer-Tropsch Synthesis.
Two process models for carbon dioxide utilized gas-to-liquids (GTL) process (CUGP) mainly producing light olefins and Fischer-Tropsch (F-T) synthetic oils were developed by Aspen Plus software. Both models are mainly composed of a reforming unit, an F-T synthesis unit and a recycle unit, while the main difference is the feeding point of fresh CO2. In the reforming unit, CO2 reforming and steam reforming of methane are combined together to produce syngas in flexible composition. Meanwhile, CO2 hydrogenation is conducted via reverse water gas shift on the Fe-based catalysts in the F-T synthesis unit to produce hydrocarbons. After F-T synthesis, the unreacted syngas is recycled to F-T synthesis and reforming units to enhance process efficiency. From the simulation results, it was found that the carbon efficiencies of both CUGP options were successfully improved, and total CO2 emissions were significantly reduced, compared with the conventional GTL processes. The process efficiency was sensitive to recycle ratio and more recycle seemed to be beneficial for improving process efficiency and reducing CO2 emission. However, the process efficiency was rather insensitive to split ratio (recycle to reforming unit/total recycle), and the optimum split ratio was determined to be zero. PMID:24933030
Zhang, Chundong; Jun, Ki-Won; Ha, Kyoung-Su; Lee, Yun-Jo; Kang, Seok Chang
An efficient synthesis of nanocrystalline MFI zeolite using different silica sources: A green approach
Nanocrystalline MFI zeolite was synthesized with a very broad range of silica to alumina ratios using an autoclave for periods of 7 h at 473 K under autogeneous pressure without seeding gel, promoter, organic solvent or sulfuric acid. The procedure has been successfully employed for the synthesis of MFI samples using fumed silica, colloidal silica, aerosil and tetraethylorthosilicate as silica sources. The synthesized samples were characterized by different techniques such as X-ray diffraction, Fourier transform infrared spectroscopy, Scanning electron microscopy. Their average crystallite size ranges from about 26 to 55 nm and they exhibit high crystallinity.
Kalita, Banani [Department of Chemistry, Gauhati University, Guwahati 781014, Assam (India); Talukdar, Anup K. [Department of Chemistry, Gauhati University, Guwahati 781014, Assam (India)], E-mail: firstname.lastname@example.com
A New and Efficient Approach to the Synthesis of Nicotine and Anabasine Analogues.
A straightforward and practical approach was established for the synthesis of nicotine and anabasine analogues by the cyclization of mesylated 1-(3-pyridinyl)-1,4, and 1,5-diol derivatives to form the pyrrolidino or piperidino fragments. Nicotine analogue (S)-15 was prepared with good enantioselectivity using the developed azacyclization procedure of nonracemic (R)-1-pyridin-3-yl-butane-1,4-diol, which was obtained by the borane-mediated reduction of ketone 12 in the presence of the spiroborate ester derived from diphenyl prolinol and ethylene glycol. PMID:20161612
Huang, Kun; Ortiz-Marciales, Margarita; De Jes�s, Melvin; Stepanenko, Viatcheslav
Efficient synthesis of chloro-derivatives of sialosyllactosylceramide, and their enhanced inhibitory effect on epidermal growth factor receptor activation
Glycosphingolipids are components of essentially all mammalian cell membranes and are involved in a variety of significant cellular functions, including proliferation, adhesion, motility and differentiation. Sialosyllactosylceramide (GM3) is known to inhibit the activation of epidermal growth factor receptor (EGFR). In the present study, an efficient method for the total chemical synthesis of monochloro- and dichloro-derivatives of the sialosyl residue of GM3 was developed. The structures of the synthesized compounds were fully characterized by high-resolution mass spectrometry and nuclear magnetic resonance. In analyses of EGFR autophosphorylation and cell proliferation ([3H]-thymidine incorporation) in human epidermoid carcinoma A431 cells, two chloro-derivatives exhibited stronger inhibitory effects than GM3 on EGFR activity. Monochloro-GM3, but not GM3 or dichloro-GM3, showed a significant inhibitory effect on ?EGFR, a splicing variant of EGFR that lacks exons 2�7 and is often found in human glioblastomas. The chemical synthesis of other GM3 derivatives using approaches similar to those described in the present study, has the potential to create more potent EGFR inhibitors to block cell growth or motility of a variety of types of cancer that express either wild-type EGFR or ?EGFR.
An efficient gel-phase synthesis of peptides on a high capacity flexible crosslinked polystyrene support: comparison with Merrifield resin.
A highly solvating copolymer was prepared in high yield by introducing a flexible crosslinker, 1,4-butanedioldimethacrylate, into the polystyrene matrix by a free radical aqueous suspension polymerization. A 2 mol% crosslinked resin showed rigidity and mechanical characteristics comparable to those of divinylbenzene-crosslinked polystyrene (Merrifield resin, DVB-PS) support. Swelling and solvation characteristics of the new resin, BDDMA-PS, were much higher than DVB-PS support in all solvents used for solid phase peptide synthesis. The diacrylate crosslinks in the resin network were found to be highly stable even after 48 h treatment with neat TFA, 6 N HCl and 6 N KOH at 110 degrees C. To demonstrate the usefulness of the new resin in high capacity peptide synthesis, a typical difficult peptide, acyl carrier protein (ACP) fragment (65-74), was synthesized on commercially available 1 mol% crosslinked DVB-PS and 2 mol% crosslinked BDDMA-PS resins under identical conditions. A protocol using NMP/DMSO mediated coupling was employed for chain assembly. The yield and purity of the product from BDDMA-PS resin was higher than when the DVB-PS resin was used. The mechanistic reason behind the synthetic efficiency of the new resin was found to be its ability to induce random coil conformation to the growing peptide chains. PMID:12043993
Krishna Kumar, M; Rajasekharan Pillai, V N; Mathew, Beena
Efficient synthesis, termination and release of RNA polymerase III transcripts in Xenopus extracts depleted of La protein.
La proteins are conserved, abundant and predominantly nuclear phosphoproteins which bind to the 3'-U termini of newly synthesized RNA polymerase III transcripts. The human La protein has been implicated in the synthesis, termination and release of such transcripts. Here we examine the potential transcriptional properties of La in Xenopus laevis, using a homologous tRNA gene as template. Immunodepletion of La from cell-free extracts leads to the formation of tRNA precursors lacking 3'-U residues. This shortening can be uncoupled from RNA polymerase III transcription, indicating that it results from nuclease degradation rather than incomplete synthesis. Extracts containing <1% of the normal La protein content synthesize tRNA precursors just as well as complete extracts, with no change in termination efficiency, and the vast majority of these full-length transcripts are not associated with the template or with residual La protein. Hence, Xenopus La seems not to function as an initiation, termination or release factor for RNA polymerase III. Consistent with the recently discovered role of La in yeast tRNA maturation in vivo, recombinant Xenopus La prevents 3'-exonucleolytic degradation of tRNA precursors in vitro. A conserved RNA chaperone function may best explain the abundance of La in eukaryotic nuclei.
Lin-Marq, N; Clarkson, S G
KF/Clinoptilolite: an efficient promoter for the synthesis of thioethers.
Potassium fluoride impregnated on natural zeolite as a new solid base system effectively catalyzes the coupling of thiophenols with electron-deficient fluoro-, chloro- and bromo-arenes in DMSO. This versatile and efficient solid base has been demonstrated to afford the corresponding desired products in good to excellent yields. This procedure provides a convenient, efficient and practical method for the preparation of diaryl thioethers. PMID:23360209
Salmanpour, Sadegh; Khalilzadeh, Mohammad A; Hosseini, Abolfazl
In Vitro Screening of Feed Resources for Efficiency of Microbial Protein Synthesis
\\u000a Recent advances in ration balancing include manipulation of feed to increase the quantity and quality of protein and energy\\u000a delivered to the small intestine. Proportionally high conversion of feed degraded in the rumen into microbial mass, i.e. a\\u000a high efficiency of microbial mass production, will lead to efficient utilization of feed nitrogen and carbon. Selection of\\u000a fibrous feeds based on
Harinder P. S. Makkar
Design and Synthesis of Efficient Fluorescent Dyes for Incorporation into DNA Backbone and Biomolecule Detection
We report here the design and synthesis of a series of ?-conjugated fluorescent dyes with D-A-D (D: donor; A: Acceptor), D-?-D, A-?-A, and D-?-A for applications as the signaling motif in biological-synthetic hybrid foldamers for DNA detection. Horner-Wadsworth-Emmons (HWE) reaction and Knoevenagel condensation were demonstrated as the optimum ways for construction of long ?-conjugated systems. Such rod-like chromophores have distinct advantages, as their fluorescence properties are not quenched by the presence of DNA. To be incorporated into the backbone of DNA, the chromophores need to be reasonably soluble in organic solvent for solid-phase synthesis, and therefore a strategy of using flexible tetra(ethylene glycol) (TEG) linkers at either end of these rod-like dyes were developed. The presence of TEG facilitates the protection of the chain-growing hydroxyl group with DMTrCl (dimethoxy trityl chloride) as well as the activation of the coupling step with phosphoramidite chemistry on an automated DNA synthesizer. To form fluorescence resonance energy transfer (FRET) pairs, six synthetic chromophores with blue to red fluorescence have been developed and those with orthogonal fluorescent emission were chosen for incorporation into DNA-chromophore hybrid foldamers.
Wang, Wei; Li, Alexander D. Q.
Efficient synthesis of methyl lycotetraoside, the tetrasaccharide constituent of the tomato defence glycoalkaloid alpha-tomatine.
Branched oligosaccharide lycotetraose, beta-D-glucopyranosyl-(1-->2)-[beta-D-xylopyranosyl-(1-->3)]-beta-D-glucopyranosyl-(1-->4)-beta-D-galactopyranose, is a key constituent of many steroidal saponins, including glycoalkaloid alpha-tomatine, which is involved in protection of plants from invading pathogens. A new synthesis of the methyl beta-lycotetraoside () is described. Key steps of the synthesis include two successive glycosylation reactions of disaccharide acceptor methyl (4,6-O-benzylidene-3-O-p-methoxybenzyl-beta-D-glucopyranosyl)-(1-->4)-2,3,6-tri-O-benzyl-beta-D-galactopyranoside with readily available benzoylated trichloroacetimidates of alpha-D-glucopyranose and alpha,beta-D-xylopyranose. This scheme allows sequential glycosylation in one-pot on account of the convenient in situ removal of a p-methoxybenzyl protecting group under the acid conditions of the first glycosylation step. Following deprotection, tetrasaccharide was obtained in 19% yield over eight steps. PMID:16106302
Jones, Nigel A; Nepogodiev, Sergey A; Field, Robert A
A highly efficient magnetic solid acid catalyst for synthesis of 2,4,5-trisubstituted imidazoles under ultrasound irradiation.
Fe(3)O(4) nanoparticles were prepared by chemical coprecipitation method and subsequently coated with 3-aminopropyltriethoxysilane (APTES) via silanization reaction. Grafting of chlorosulfuric acid on the amino-functionalized Fe(3)O(4) nanoparticles afforded sulfamic acid-functionalized magnetic nanoparticles (SA-MNPs). SA-MNPs was found to be a mild and effective solid acid catalyst for the efficient, one-pot, three-component synthesis of 2,4,5-trisubstituted imidazoles under ultrasound irradiation. This protocol afforded corresponding imidazoles in shorter reaction durations, and in high yields. This green procedure has many obvious advantages compared to those reported in the previous literatures, including avoiding the use of harmful catalysts, easy and quick isolation of the products, excellent yields, short routine, and simplicity of the methodology. PMID:23137656
Safari, Javad; Zarnegar, Zohre
Rational Design and Synthesis of Freestanding Photoelectric Nanodevices as Highly Efficient Photocatalysts
Photocatalysts are of significant interest for solar energy harvesting and conversion into chemical energy. However, the photocatalysts available to date are limited by either poor efficiency in the visible light range or insufficient photoelectrochemical stability. Here we report the rational design of a new generation of freestanding photoelectric nanodevices as highly efficient and stable photocatalysts by integrating a nanoscale photodiode with two redox catalysts in a single nanowire heterostructure. We show that a platinum-silicon-silver nanowire heterostructure can be synthesized to integrate a nanoscale metal-semiconductor Schottky diode encased in a protective insulating shell with two exposed metal catalysts. We further demonstrated that the Schottky diodes exhibited pronounced photovoltaic effect with nearly unity internal quantum efficiency, and that the integrated nanowire heterostructures could be used as highly efficient photocatalysts for a wide range of thermodynamically downhill and uphill reactions including photocatalytic degradation of organic dyes, reduction of metal ions and carbon dioxide using visible light. Our studies for the first time demonstrated the integration of multiple distinct functional components into a single nanostructure to form a standalone active nanosystem, and for the first time successfully realized a photoelectric nanodevice that is both highly efficient and highly stable throughout the entire solar spectrum. It thus opens a rational avenue to design and synthesize a new generation of photoelectric nanosystems with unprecedented efficiency and stability, and will impact broadly in areas including environmental remediation and solar fuel production.
Qu, Yongquan; Liao, Lei; Cheng, Rui; Wang, Yue; Lin, Yung-chen; Huang, Yu; Duan, Xiangfeng
Facile and Efficient Synthesis of 14?Alkyl? or Aryl?14?H?Dibenzo[a,j]xanthenes using Sulfonyl?Functionalized Ionic Liquids
An efficient, simple, and rapid synthesis of 14?alkyl?or aryl?14?H?dibenzo[a,j]xanthenes is reported by one?pot condensation of 2?naphthol with alkyl or aryl aldehydes in the presence of sulfonyl?functionalized acidic ionic liquids at 125�C.
Pratibha Kumari; Vinith Yathindranath; S. M. S. Chauhan
Reaction between isocyanides and chalcones: an efficient solvent-free synthesis of 5-hydroxy-3,5-diaryl-1,5-dihydro-2 H-pyrrol-2-ones
A simple and efficient synthesis of 5-hydroxy-3,5-diaryl-1,5-dihydro-2H-pyrrol-2-ones is described. Heating a mixture of an isocyanide and a 1,3-diaryl-2-propen-1-one under solvent-free conditions produces the title compounds in good to excellent yields.
Mehdi Adib; Mohammad Mahdavi; Mahsa Alizadeh Noghani; Hamid Reza Bijanzadeh
Bifunctionalized allenes. Part XIII. A convenient and efficient method for regioselective synthesis of phosphorylated ?-hydroxyallenes with protected and unprotected hydroxy group.
The paper describes a convenient and efficient method for regioselective synthesis of phosphorylated ?-hydroxyallenes using an atom economical [2,3]-sigmatropic rearrangement of intermediate propargyl phosphites or phosphinites. These can be readily prepared via reaction of protected alkynols with dimethyl chlorophosphite or chlorodiphenyl phosphine respectively in the presence of a base. PMID:24840901
Ismailov, Ismail E; Ivanov, Ivaylo K; Christov, Valerij Ch
Highly efficient and versatile synthesis of lactams and N-heterocycles via Al(OTf)3-catalyzed cascade cyclization and ionic hydrogenation reactions.
The discovery and development of an efficient and versatile method for the synthesis of N-substituted lactams is described. Pyrrolindinones, piperidones, and structurally related heterocycles were formed by Al(OTf)3-catalyzed cascade cyclization and ionic hydrogenation reactions of corresponding nitrogen substituted ketoamides in good yields. PMID:24313882
Qi, Jianguo; Sun, Chenbin; Tian, Yulin; Wang, Xiaojian; Li, Gang; Xiao, Qiong; Yin, Dali
Indium(III) iodide-mediated Strecker reaction in water: an efficient and environmentally friendly approach for the synthesis of ?-aminonitrile via a three-component condensation
A mild, efficient and environmentally friendly method has been developed for the synthesis of ?-aminonitriles via a three-component condensation of aldehyde, amine and TMSCN in the presence of a catalytic amount of indium(III) iodide in water. The reactions proceeded smoothly at room temperature in water to generate the corresponding products in moderate to excellent yields.
Zhi-Liang Shen; Shun-Jun Ji; Teck-Peng Loh
Highly efficient one-pot synthesis of N-sulfonylamidines by Cu-catalyzed three-component coupling of sulfonyl azide, alkyne, and amine.
A highly efficient, mild, practical, and catalytic multicomponent reaction for the synthesis of N-sulfonylamidines has been developed. This reaction has an extremely wide scope with regard to all three coupling components of alkyne, sulfonyl azide, and amine. Two plausible mechanistic pathways involving ketenimine or triazole intermediate are tentatively presented for the copper-catalyzed three-component coupling reactions. PMID:15713069
Bae, Imhyuck; Han, Hoon; Chang, Sukbok
Silica tungstic acid as an efficient and reusable catalyst for the one-pot synthesis of 2-amino-4H-chromene derivatives.
Silica tungstic acid (STA) has been found to be an efficient and reusable solid acid catalyst for the synthesis of 2-amino-4H-chromenes via the three-component reaction of aromatic aldehydes, malononitrile, and ?-naphthol. STA as a novel solid acid was characterized by X-ray fluorescence, X-ray diffraction, and Fourier transform infrared spectroscopy. PMID:24664332
Farahi, Mahnaz; Karami, Bahador; Alipour, Samambar; Moghadam, Leila Taghavi
Synthesis of multifunctional PAMAM-aminoglycoside conjugates with enhanced transfection efficiency.
The development of multifunctional vectors for efficient and safe gene delivery is one of the major challenges for scientists working in the gene therapy field. In this context, we have designed a novel type of aminoglycoside-rich dendrimers with a defined structure based on polyamidoamine (PAMAM) in order to develop efficient, nontoxic gene delivery vehicles. Three different conjugates, i.e., PAMAM G4-neamine, -paromomycin, and -neomycin, were synthesized and characterized by nuclear magnetic resonance (NMR) and MALDI analysis. The conjugates were found to self-assemble electrostatically with plasmid DNA, and unlike neamine conjugate, each at its optimum showed increased gene delivery potency compared to PAMAM G4 dendrimer in three different cell lines, along with negligible cytotoxicity. These results all disclosed aminoglycosides as suitable functionalities for tailoring safe and efficient multifunctional gene delivery vectors. PMID:24147798
Ghilardi, Alessandra; Pezzoli, Daniele; Bellucci, Maria Cristina; Malloggi, Chiara; Negri, Armando; Sganappa, Aurora; Tedeschi, Gabriella; Candiani, Gabriele; Volonterio, Alessandro
An efficient and recyclable catalyst for the cleavage of tert-butyldiphenylsilyl ethers.
An efficient, chemoselective, and environment-friendly method for the deprotection of tert-butyldiphenylsilyl ethers mediated by triflic acid supported on silica gel is reported. A wide range of tert-butyldiphenylsilyl ethers derived from carbohydrate and saponin residues can be smoothly cleaved in the presence of various types of other protecting groups in good to excellent yields in acetonitrile. This heterogeneous reaction does not require aqueous workup, and the supported catalyst can be readily recycled. PMID:22565030
Yan, Shiqiang; Ding, Ning; Zhang, Wei; Wang, Peng; Li, Yingxia; Li, Ming
Coordinated synthesis of multimachine power system stabilizer using an efficient decentralized modal control (DMC) algorithm
This paper presents a new method for simultaneously selecting the power system stabilizer (PSS) parameters in multimachine power systems. Design of local output feedback power system stabilizer using local signal of the generator (e.g. speed or power) is formulated as a decentralized modal control (DMC) problem. Exact model reduction based on modal control theory is proposed to make the determination of PSS parameters highly efficient. Results obtained from the coordinated tuning of the parameters of three power system stabilizers equipped on a multimachine power system show that exact assignment of the eigenvalues associated with the poorly damped electromechanical modes can be achieved in a very efficient manner.
Chen, C.; Hsu, Y.
An Efficient Synthesis of the Fully Elaborated Isoindolinone Unit of Muironolide A
An efficient stereocontrolled construction of the fully substituted isoindolone subunit of muironolide A is described. The approach is centered on the intramolecular Diels-Alder reaction between the enol form of the ?-keto amide and an ? ? ? ?-unsaturated ester, followed by the installation of the cyclohexene double bond.
Xiao, Qing; Young, Kyle
Synthesis and Energy Transfer Efficiency of FRET Terminators Derived from Different Linkers
A number of different energy transfer dye labeled-cassettes were synthesized using aminoacid based trifunctional linkers and coupled to the propargylamino-substituted dideoxynucleoside-5?-triphosphates (ddNTPs). These terminators were evaluated for their energy transfer efficiency and DNA sequencing potential using thermostable DNA polymerase.
Shiv Kumar; Satyam Nampalli; Patrick J. Finn; T. Sudhakar Rao; Chung-Yuan Chen; Parke K. Flick; Carl W. Fuller
Efficient synthesis of tailored magnetic carbon nanotubes via a noncovalent chemical route.
We report here an efficient noncovalent chemical route to dense and uniform assembly of magnetic nanoparticles onto multi-walled carbon nanotubes within a single-layer configuration. While preserving the electrical conduction behavior of the nanotube network itself, the resulting carbon nanotube derivatives exhibit a distinct superparamagnetism, and can be magnetically manipulated via a quick and reversible mode. PMID:21116557
Li, Xianglong; Thompson, Joe D; Zhang, Yingying; Brady, Christina I; Zou, Guifu; Mack, Nathan H; Williams, Darrick; Duque, Juan G; Jia, Quanxi; Doorn, Stephen K
A New and Efficient Synthesis of ?-Amino Cycloalkyl-Phosphonic Acids via Electrophilic Azidation of Cycloalkylphosphonates
?-Amino cyclobutyl-, cyclopentyl-and cyclohexylphosphonic acids (13) were efficiently prepared from the related unsubstituted cycloalkylphosphonates (5), in three steps including electrophilic azidation of the corresponding lithiated carbanions, catalytic hydrogenation of the intermediate ?-azido cycloalkyl-phosphonates (10) and acidic hydrolysis of the resulting ?-amino cycloalkyl-phosphonates (12).
Catherine Gu�guen; No�l Collignon; Philippe Savignac
Efficient synthesis of fluorescent-PET probes based on [(18)F]BODIPY dye.
We report the direct conversion of fluorescent probes to PET/fluorescent probes after efficient [(19)F]/[(18)F] exchange at the BODIPY motif. The radiolabeling of a NIR BODIPY dye was also established, which was conjugated with the RGD peptide for PET/fluorescence imaging of integrin expression in vivo. PMID:24869927
Liu, Shuanglong; Li, Dan; Zhang, Zhe; Surya Prakash, G K; Conti, Peter S; Li, Zibo
Design and synthesis of harzialactone analogues: promising anticancer agents.
New homologues of harzialactone were synthesized using D-glucose as chiral template. Wittig reaction to introduce aromatic moiety in 10 and chemoselective anomeric oxidation of 13 were used as key reactions in our synthesis. Anticancer activity of these target molecules was assessed against five cancer cell lines, P388D1, HL60, COLO-205, Zr-75-1 and HeLa. Both compound 5 and 6, showed significant activity against colon cancer (COLO-205) and cervical cancer (HeLa) and moderate with others. To the best of our knowledge, this is the first report of harzialactone analogues as potent inhibitors of human colon and cervical cancer. PMID:21074431
Pawar, Vishwas U; Ghosh, Sougata; Chopade, Balu A; Shinde, Vaishali S
Direct synthesis of high-density lead sulfide nanowires on metal thin films towards efficient infrared light conversion
We report chemical-vapor-deposition (CVD) synthesis of high-density lead sulfide (PbS) nanowire arrays and nano pine trees directly on Ti thin films, and the fabrication of photovoltaic devices based upon the PbS nanowires. The as-grown nanowire arrays are largely vertically aligned to the substrates and are uniformly distributed over a relatively large area. Field effect transistors incorporating single PbS nanowires show p-type conduction and high mobilities. These catalytic metal thin films also serve as photocarrier collection electrodes and greatly facilitate device integration. For the first time, we have fabricated Schottky junction photovoltaic devices incorporating PbS nanowires, which demonstrate the capability of converting near-infrared light to electricity. The PbS nanowire devices are stable in air and their external quantum efficiency shows no significant decrease over a period of 3 months in air. We have also compared the photocurrent direction and quantum efficiencies of photovoltaic devices made with different metal electrodes, and the results are explained by band bending at the Schottky junction. Our research shows that PbS nanowires are promising building blocks for collecting near-infrared solar energy.
Wu, Hengkui; Yang, Yiming; Oh, Eunsoon; Lai, Fachun; Yu, Dong
High-resolution analysis of DNA synthesis start sites and nucleosome architecture at efficient mammalian replication origins.
DNA replication origins are poorly characterized genomic regions that are essential to recruit and position the initiation complex to start DNA synthesis. Despite the lack of specific replicator sequences, initiation of replication does not occur at random sites in the mammalian genome. This has lead to the view that DNA accessibility could be a major determinant of mammalian origins. Here, we performed a high-resolution analysis of nucleosome architecture and initiation sites along several origins of different genomic location and firing efficiencies. We found that mammalian origins are highly variable in nucleosome conformation and initiation patterns. Strikingly, initiation sites at efficient CpG island-associated origins always occur at positions of high-nucleosome occupancy. Origin recognition complex (ORC) binding sites, however, occur at adjacent but distinct positions marked by labile nucleosomes. We also found that initiation profiles mirror nucleosome architecture, both at endogenous origins and at a transgene in a heterologous system. Our studies provide a unique insight into the relationship between chromatin structure and initiation sites in the mammalian genome that has direct implications for how the replication programme can be accommodated to diverse epigenetic scenarios. PMID:23995398
Lombra�a, Rodrigo; Almeida, Ricardo; Revuelta, Isabel; Madeira, Sofia; Herranz, Gonzalo; Saiz, N�stor; Bastolla, Ugo; G�mez, Mar�a
Efficient synthesis of DNA dumbbells using template-induced chemical ligation in double-stranded polynucleotides closed by minihairpin fragments.
The chemical ligation of 17 50-54-membered nicked DNA dumbbells with different closing fragments, nick positions, and nucleotides facing the nick were investigated. T4, T5, GTA4C, GCGA2GC, and GCGA3GC sequences were chosen as the closing fragments. The nicks were placed in the center of the duplex stem or were adjacent to the closing fragments. N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide and cyanogen bromide were used as the condensing agents. We showed that the ligation efficiency is 10%-90% depending on the sequence of the closing fragments, nick position, and nucleotides facing the nick. Coupling yields of 80%-90% were observed when the nick was situated in the middle of the molecule between two T residues or was adjacent to GCGA2GC or GCGA3GC minihairpins. In the last case, the reacting 3'-phosphate and 5'-hydroxy groups were brought close together by only two base pair minihairpins. The coupling yields did not depend on the nature of the condensing agent. On the basis of the results obtained, we believe a rational design of nicked DNA dumbbells has been developed for efficient chemical synthesis of closed dumbbells. PMID:10192294
Kuznetsova, S A; Merenkova, I N; Kanevsky, I E; Shabarova, Z A; Blumenfeld, M
Synthesis of a Highly Efficient BiOCl Single-Crystal Nanodisk Photocatalyst with Exposing {001} Facets.
BiOCl is known as a highly efficient photocatalyst for degradation of pollutants. However, effective methods for fabricating BiOCl nanomaterials with well-defined facets are still lacking. In this work, a facile synthetic method was developed for the fabrication of BiOCl nanodisks with exposed {001} facets. The central feature of this approach was the use of water as the hydrolysis agent and ethylene glycol as the crystal growth inhibitor agent to tune the growth of BiOCl nanomaterial. With this approach, the size and shape of BiOCl nanostructures could be effectively tuned through adjusting the volume ratio of ethylene glycol/H2O. In addition, the mechanism of the crystal growth in this fabrication process was elucidated. The as-prepared BiOCl nanodisks with exposed {001} facets exhibited an excellent photocatalytic activity towards Rhodamine B degradation under both ultraviolet and visible light irradiations. These findings shed light on the deep understanding of formation mechanisms of BiOCl nanodisks and provide an efficient and facile method for the synthesis of high active photocatalyst. PMID:24797177
Zhang, Xing; Wang, Xin-Bo; Wang, Li-Wei; Wang, Wei-Kang; Long, Lu Lu; Li, Wen-Wei; Yu, Han-Qing
Green synthesis of highly efficient CdSe quantum dots for quantum-dots-sensitized solar cells
Green synthesis of CdSe quantum dots for application in the quantum-dots-sensitized solar cells (QDSCs) is investigated in this work. The CdSe QDs were prepared with glycerol as the solvent, with sharp emission peak, full width at half maximum around 30 nm, and absorption peak from 475 nm to 510 nm. The reaction is environmental friendly and energy saving. What's more, the green synthesized CdSe QDs are coherence to the maximum remittance region of the solar spectrum and suitable as sensitizers to assemble onto TiO2 electrodes for cell devices application. What's more, the dynamic procedure of the carriers' excitation, transportation, and recombination in the QDSCs are discussed. Because the recombination of the electrons from the conduction band of TiO2's to the electrolyte affects the efficiency of the solar cells greatly, 3-Mercaptopropionic acid capped water-dispersible QDs were used to cover the surface of TiO2. The resulting green synthesized CdSe QDSCs with Cu2S as the electrode show a photovoltaic performance with a conversion efficiency of 3.39%.
Gao, Bing; Shen, Chao; Zhang, Bo; Zhang, Mengya; Yuan, Shuanglong; Yang, Yunxia; Chen, Guorong
Manganese-Mediated Carbon-Carbon Bond Formation in Aqueous Media: Chemoselective Allylation and Pinacol Coupling of Aryl Aldehydes.
The use of manganese as a mediator for allylations and pinacol couplings in aqueous media was investigated. The combination of manganese and copper is found to be a highly effective mediator for the allylation of aryl aldehydes in water. Such a combination is found to be more reactive than other previously reported metals in aqueous media. No reaction was observed with either manganese or copper alone as the mediator. Only a catalytic amount of copper is required for the proceeding of the reaction. The uses of Cu(0), Cu(I), and Cu(II) as the copper source are all effective. The use of a catalytic amount of manganese combined with a stoichoimetric amount of copper led to the failure of the reaction. Allyl chloride is found to be more effective than allyl bromide for the corresponding reaction. The use of substituted allyl halides gave a mixture of regio- and diastereoisomers. Aromatic aldehydes reacted chemoselectively in the presence of aliphatic aldehydes. An exclusive selectivity was also observed when both an aliphatic and an aromatic aldehyde functionalities are present in the same molecule. In the presence of acetic acid or ammonium chloride, manganese was found to effect the pinacol-coupling reaction in water. The reaction proceeds selectively with aryl aldehydes. PMID:11672403
Li, Chao-Jun; Meng, Yue; Yi, Xiang-Hui; Ma, Jihai; Chan, Tak-Hang
Synthesis of nitrogen-doped porous carbon nanofibers as an efficient electrode material for supercapacitors.
Supercapacitors (also known as ultracapacitors) are considered to be the most promising approach to meet the pressing requirements of energy storage. Supercapacitive electrode materials, which are closely related to the high-efficiency storage of energy, have provoked more interest. Herein, we present a high-capacity supercapacitor material based on the nitrogen-doped porous carbon nanofibers synthesized by carbonization of macroscopic-scale carbonaceous nanofibers (CNFs) coated with polypyrrole (CNFs@polypyrrole) at an appropriate temperature. The composite nanofibers exhibit a reversible specific capacitance of 202.0 F g(-1) at the current density of 1.0 A g(-1) in 6.0 mol L(-1) aqueous KOH electrolyte, meanwhile maintaining a high-class capacitance retention capability and a maximum power density of 89.57 kW kg(-1). This kind of nitrogen-doped carbon nanofiber represents an alternative promising candidate for an efficient electrode material for supercapacitors. PMID:22769051
Chen, Li-Feng; Zhang, Xu-Dong; Liang, Hai-Wei; Kong, Mingguang; Guan, Qing-Fang; Chen, Ping; Wu, Zhen-Yu; Yu, Shu-Hong
An efficient synthesis of 2-benzoxepines from Morita-Baylis-Hillman adducts using heterogeneous recyclable catalysts.
2-Benzoxepines have efficiently been synthesized from Morita-Baylis-Hillman adducts, alkyl 3-aryl-3-hydroxy-2-methylenepropanoates by treatment with HCHO catalyzed by silica supported perchloric acid (HClO4.SiO2) or Amberlyst-15 in CH2Cl2 under reflux for a short period of time (1.5-2.5 h). The catalyst can be recovered and recycled. The antibacterial properties of the new 2-benzoxepines were studied but no activity was found. PMID:16508203
Das, Biswanath; Majhi, Anjoy; Banerjee, Joydeep; Chowdhury, Nikhil; Holla, Harish; Harakishore, Kankipati; Murty, Upadhayula Suryanarayana
Efficient synthesis of carbazolespirooxindole skeletons via asymmetric Diels-Alder reaction of 3-vinylindoles and methyleneindolinones.
A highly efficient catalytic asymmetric Diels-Alder reaction between 3-vinylindoles and methyleneindolinones has been achieved using chiral N,N'-dioxide-Ni(ii) complexes as the catalysts. A wide variety of substrates were readily tolerated, generating exclusively the corresponding exo-carbazolespirooxindole derivatives in excellent yields with high enantiomeric excesses (up to 98% yield, >99?:?1 d.r., and 98% ee) under mild reaction conditions. PMID:24967917
Zheng, Haifeng; He, Peng; Liu, Yangbin; Zhang, Yulong; Liu, Xiaohua; Lin, Lili; Feng, Xiaoming
Synthesis of Plantago Psyllium Mucilage Grafted Polyacrylamide and its Flocculation Efficiency in Tannery and Domestic Wastewater
A graft copolymer of P.psyllium mucilage and polyacrylamide has been synthesized in the presence of nitrogen using ceric ion-nitric acid redox initiator. This grafted copolymer was tested for its flocculation efficiency in Tannery and Domestic wastewater by the standard Jar Test method. The effects of polymer concentration, contact time and pH on percent removal of solid wastes from Tannery and
Monika Agarwal; Rajani Srinivasan; Anuradha Mishra
Efficient chemoenzymatic synthesis of globotriose and its derivatives with a recombinant ?-(1?4)-galactosyltransferase
A truncated ?-(1?4)-galactosyltransferase (LgtC) gene from Neisseria meningitidis was cloned. The recombinant glycosyltransferase was expressed in Escherichia coli BL21 (DE3) strain with high specific activity (5 units\\/mg protein). Its acceptor specificity was carefully characterized. Then the purified enzyme was utilized in highly efficient syntheses of globotriose and a variety of ?-(1?4)-galactosylated derivatives as potential antibacterial agents.
Jianbo Zhang; Przemyslaw Kowal; Jianwen Fang; Peter Andreana; Peng George Wang
Efficient chemoenzymatic synthesis of globotriose and its derivatives with a recombinant alpha-(1-->4)-galactosyltransferase.
A truncated alpha-(1-->4)-galactosyltransferase (LgtC) gene from Neisseria meningitidis was cloned. The recombinant glycosyltransferase was expressed in Escherichia coli BL21 (DE3) strain with high specific activity (5 units/mg protein). Its acceptor specificity was carefully characterized. Then the purified enzyme was utilized in highly efficient syntheses of globotriose and a variety of alpha-(1-->4)-galactosylated derivatives as potential antibacterial agents. PMID:12039536
Zhang, Jianbo; Kowal, Przemyslaw; Fang, Jianwen; Andreana, Peter; Wang, Peng George
Uniformity's influence of silica xerogel on synthesis efficiency of SiC nanorods by carbothermal reduction
Silica xerogels containing nanocarbon were milled for several hours before the carbothermal reduction processing. The formation of SiC nanorods was investigated at different annealing temperatures. It is shown that the formation temperature of SiC nanorods can be decreased if the powder size of milled silica xerogels is lower than 100 nm. The morphology, structure and production efficiency of synthesized SiC
Huynh Thi Ha; Cao Tuan Anh; Nguyen Thi Thu Ha; Phan Viet Phong; Dao Tran Cao; Le Quang Huy; Nguyen The Quynh
A new and efficient method for the synthesis of Ulipristal acetate.
In this study, we describe another new and efficient route for preparing Ulipristal acetate. The 1,4-addition compound 5 was greatly improved after the starting material ketone 1 was underwent epoxidation, cyanation, hydroxyl group protection and Grignard addition. The synthetic procedure is only 6 steps and the total yield is about 27.4%, which is much suitable for industrial process. PMID:24686204
Cheng, Xu; Li, Xiaocen; Duan, Yanjun; Yu, Yongguo; Hai, Li; Wu, Yong
Efficient synthesis of S-linked glycopeptides in aqueous solution by a convergent strategy.
In naturally occurring glycopeptides and glycoproteins the glycan residues generally possess N- and O-linkages to the peptide backbone. Here we report the synthesis of the corresponding S-linked glycopeptides by a convergent strategy to provide compounds which should be quite stable to glycosidases. To this end, peptides that contain beta-bromoalanine and gamma-bromohomoalanine were generated either directly by bromination of serine and homoserine residues, respectively, or by standard ligation of the corresponding amino acids. 1-Thiosugars of O-acetyl protected GalNAc, GlcNAc, and lactose were prepared by known procedures. Reaction of the thiosugars with these peptides in an ethyl acetate/water two-phase system, which contained TBAHS and NaHCO(3), or in a one-phase system that consists of DMF/water and which contains NaHCO(3), led to the desired S-linked glycopeptides cleanly and in almost quantitative yield. This reaction also worked well for O-unprotected 1-thiosugars. PMID:14978813
Zhu, Xiangming; Schmidt, Richard R
Efficient synthesis of pure monotosylated beta-cyclodextrin and its dimers.
6-O-Monotosyl-?-cyclodextrin (mono-Ts-?CD) is one of the most important intermediates in the production of substituted ?CD. So far, performing the monotosylation reaction and, in particular, the purification steps was challenging, relied on toxic solvents, and resulted in long and expensive procedures at, importantly, low yields. Here, the reaction of cyclodextrin with p-toluenesulfonyl chloride in aqueous environment is described to obtain a highly pure mono-Ts-?CD, for which a single-step purification with a cation exchange resin was applied. With this synthetic route and purification, yields could be increased from typically <10-15% to 35%, and organic solvents could be avoided. As characterized by FTIR, mass spectrometry, elemental analysis, and NMR, mono-Ts-?CD was obtained with a molar purity of >98mol%. From mono-Ts-?CD, ?-cyclodextrin dimers linked by ethylenediamine (bis-Et-?CD) were successfully prepared (yield 93%, purity 96mol%) in a one-step approach using an anion exchange resin to trap leaving groups that typically interfere in the reaction. This synthesis procedure with a direct collection of side-products may be a general strategy applicable for nucleophilic substitution of tosylated cyclodextrins. PMID:24060538
Tripodo, Giuseppe; Wischke, Christian; Neffe, Axel T; Lendlein, Andreas
DNA mismatch repair efficiency and fidelity are elevated during DNA synthesis in human cells
DNA mismatch repair (MMR) within human cells is hypothesized to occur primarily at the replication fork. However, experimental models measuring MMR activity at specific phases of the cell cycle and during genomic DNA synthesis are lacking. We have investigated MMR activity within the nuclear environment of HeLa cells after enriching for G1, S and G2/M phase of the cell cycle by centrifugal elutriation. This approach preserves physiologically normal MMR activity in cell populations subdivided into different phases of the cell cycle. Here we have shown that nuclear protein concentration of hMutS? and hMutL? increases as cells progress into S phase during routine cell culture. MMR activity, as measured by both in vitro and in vivo approaches, increases during S phase to the highest extent within normally growing cells. Both fidelity and activity of MMR are highest on actively replicating templates within intact cells during S phase. The MMR pathway however, is also active at lower levels at other phases of the cell cycle, and on nonreplicating templates.
Edelbrock, Michael A.; Kaliyaperumal, Saravanan; Williams, Kandace J.
Microwave-assisted efficient synthesis of 2-hydroxydeoxybenzoins from the alkali degradation of readily prepared 3-aryl-4-hydroxycoumarins in water.
This paper describes an operationally simple, green and efficient approach for the synthesis of 2-hydroxydeoxybenzoins bearing diverse substituents from the microwave-assisted alkali degradation of 3-aryl-4-hydroxycoumarins in water. The latter compounds were readily prepared from the intramolecular Claisen condensation reaction of methyl 2-(2-arylacetoxy)benzoates in the presence of Cs2CO3-acetone, in excellent yields and without laborious workup procedures. This method is highly atom-economic and thus applicable for the large-scale synthesis of 2-hydroxydeoxybenzoins. PMID:24189303
Zhou, Zhong-Zhen; Yan, Guang-Hua; Chen, Wen-Hua; Yang, Xue-Mei
Polyvinyl alcohol: an efficient fuel for synthesis of superparamagnetic LSMO nanoparticles for biomedical application.
La(0.7)Sr(0.3)MnO(3) (LSMO) nanoparticles have been prepared using glycine and polyvinyl alcohol (PVA) as fuels. Their crystal structure, particle morphology and compositions are characterized using X-ray diffraction, transmission electron microscopy, field-emission electron microscopy and energy dispersive analysis of X-ray. They show a pseudo-cubic perovskite structure. The spherical particle sizes of 30 and 20 nm have been obtained from samples prepared by glycine and PVA respectively. The field cooled (FC) and zero field cooled (ZFC) magnetizations have been recorded from 5 to 375 K at 500 Oe and superparamagnetic blocking temperatures (T(B)) of 75 and 30 K are obtained from samples prepared by glycine and PVA respectively. Particle size distribution is observed from dynamic light scattering measurements. Dispersion stability of the particles in water is studied by measuring the Zeta potential with varying the pH of the medium from 1 to 12. Under induction heating experiments, a hyperthermia temperature (42-43 �C) is achieved by both the samples (3-6 mg mL(-1)) at magnetic fields of 167-335 Oe and at a frequency of 267 kHz. The bio-compatibility of the LSMO nanoparticles is studied on the L929 and HeLa cell lines by MTT assay for up to 48 h. The present work reveals the importance of synthesis technique and fuel choice on structural, morphological, magnetic, hyperthermia and biocompatible properties of LSMO and predicts the suitability for biomedical applications. PMID:22277953
Thorat, N D; Shinde, K P; Pawar, S H; Barick, K C; Betty, C A; Ningthoujam, R S
Electrochemical synthesis of Cu/ZnO nanocomposite films and their efficient field emission behaviour
The Cu/ZnO nanocomposite films have been synthesized by cathodic electrodeposition and characterized using X-ray diffractometer (XRD), scanning electron microscope (SEM), transmission electron microscope (TEM), photoluminescence (PL) and field emission microscope (FEM). The XRD pattern shows a set of well defined diffraction peaks, which could be indexed to the wurtzite hexagonal phase of ZnO. In addition, characteristic diffraction peaks corresponding to Cu and Zn are also observed. The SEM image shows formation of two-dimensional (2D) hexagonal sheets randomly distributed and aligned almost normal to the substrate. Uniformly distributed small clusters of Cu nanoparticles possessing average diameter of �25 nm, as revealed from the TEM image, are seen to be present on these 2D ZnO sheets. The selected area electron diffraction (SAED) image confirms the nanocrystalline nature of the Cu particles. From the field emission studies, carried out at the base pressure of �1 � 10 -8 mbar, the turn-on field required for an emission current density of 0.1 ?A/cm 2 is found to be 1.56 V/?m and emission current density of �100 ?A/cm 2 has been drawn at an applied field of 3.12 V/?m. The Cu/ZnO nanocomposite film exhibits good emission current stability at the pre-set value of �10 ?A over a duration of 5 h. The simplicity of the synthesis route coupled with the better emission properties propose the electrochemically synthesized Cu/ZnO nanocomposite film emitter as a promising electron source for high current density applications.
Jamali Sheini, Farid; Singh, Jai; Srivasatva, O. N.; Joag, Dilip S.; More, Mahendra A.
Efficiency at L-Band on the Expanded Very Large Array Synthesis Telescope
A primary goal of the Very Large Array Expansion (EVLA - Phase 1) Project is to provide continuous frequency coverage with increased sensitivity from 1 to 50 GHz from the secondary focus. Eight receiver bands were chosen to cover the above range. The lower three bands cover the 1-8 GHz range, with each receiver covering an octave band (1-2, 2-4 and 4-8 GHz). A new feed cone has been designed for the EVLA antenna to accommodate the eight receivers and feeds. The feeds for the lower three bands use the compact feed design [1], [2], which is relatively small compared to the linear taper design for the same illumination taper. The design of the L-band feed was critical as its size dictated the layout of the feeds on the feed cone. The feed layout was driven by two factors: (i) the phase center of the feed at mid-band needs to be at or near the secondary focus and (ii) the larger feeds do not cause blockage for the adjacent feeds. In order to achieve these goals, a compromise was made on the size of the L-band feed, resulting in a small loss in efficiency. The calculated aperture efficiency varied between 0.46 and 0.62. Spillover temperatures at 1.4 GHz and 2.0 GHz were 12.3 K and 12 K, respectively. However, measurements on the antenna gave lower efficiencies and spillover temperatures. The cause of this discrepancy has been analyzed and is presented here.
Srikanth, S.; Perley, R.; Hayward, R.; Mertely, D.
Synthesis, photoconductivity, and photogeneration efficiency of polysiloxanes bearing hole-conductors for photorefractive materials
Two series of polysiloxanes, namely, PSX-DCZ and PSX-TPD, with hole-transporting moieties have been synthesized and their electronic absorption, electrochemical behavior, quantum efficiency of charge generation, and photoconductivity is also studied. Our results show that the photocurrent were found to be ca. 3280nA for PSX-DCZ\\/C60 and ca. 3400nA for the PSX-TPD\\/C60 at wavelength of 633nm and an electric field of 60V\\/?m.
In Kyu Moon; Jin-Woo Oh; Nakjoong Kim
Designed synthesis of uniformly sized iron oxide nanoparticles for efficient magnetic resonance imaging contrast agents.
Various magnetic nanoparticles have been extensively investigated as novel magnetic resonance imaging (MRI) contrast agents owing to their unique characteristics, including efficient contrast effects, biocompatibility, and versatile surface functionalization capability. Nanoparticles with high relaxivity are very desirable because they would increase the accuracy of MRI. Recent progress in nanotechnology enables fine control of the size, crystal structure, and surface properties of iron oxide nanoparticles. In this tutorial review, we discuss how MRI contrast effects can be improved by controlling the size, composition, doping, assembly, and surface properties of iron-oxide-based nanoparticles. PMID:22138852
Lee, Nohyun; Hyeon, Taeghwan
Synthesis and characterization of VO2-based thermochromic thin films for energy-efficient windows
Thermochromic VO2 thin films have successfully been grown on SiO2-coated float glass by reactive DC and pulsed-DC magnetron sputtering. The influence of substitutional doping of V by higher valence cations, such as W, Mo, and Nb, and respective contents on the crystal structure of VO2 is evaluated. Moreover, the effectiveness of each dopant element on the reduction of the intrinsic transition temperature and infrared modulation efficiency of VO2 is discussed. In summary, all the dopant elements--regardless of the concentration, within the studied range-- formed a solid solution with VO2, which was the only compound observed by X-ray diffractometry. Nb showed a clear detrimental effect on the crystal structure of VO2. The undoped films presented a marked thermochromic behavior, specially the one prepared by pulsed-DC sputtering. The dopants effectively decreased the transition of VO2 to the proximity of room temperature. However, the IR modulation efficiency is markedly affected as a consequence of the increased metallic character of the semiconducting phase. Tungsten proved to be the most effective element on the reduction of the semiconducting-metal transition temperature, while Mo and Nb showed similar results with the latter being detrimental to the thermochromism.
Efficient, highly diastereoselective MS 4 ?-promoted one-pot, three-component synthesis of 2,6-disubstituted-4-tosyloxytetrahydropyrans via Prins cyclization
Summary A simple, efficient and highly diastereoselective one-pot three-component synthesis of functionalized 2,6-disubstituted-4-tosyloxytetrahydropyrans was performed. The synthesis features an optimized Prins cyclization in which an aromatic homoallylic alcohol, an aromatic/aliphatic aldehyde, and p-toluenesulfonic acid (catalyst and reagent) are reacted in the presence of molecular sieves (MS) 4 � at reflux in dichloromethane to afford excellent yields (72�96%) within short reaction times (20�90 min). The MS 4 �-promoted synthesis proved to be versatile enough to provide an array of symmetrical and unsymmetrical tetrahydropyran derivatives in economical manner. Furthermore, cleavage of the 4-tosyl group under mild conditions afforded 4-hydroxytetrahydropyran in excellent yields (95�96%).
Konduru, Naveen Kumar
Renewable rigid diamines: efficient, stereospecific synthesis of high purity isohexide diamines.
We report an efficient three-step strategy for synthesizing rigid, chiral isohexide diamines derived from 1,4:3,6-dianhydrohexitols. These biobased chiral building blocks are presently the subject of several investigations (in our and several other groups) because of their application in high-performance biobased polymers, such as polyamides and polyurethanes. Among the three possible stereo-isomers, dideoxy-diamino isoidide and dideoxy-diamino isosorbide can be synthesized from isomannide and isosorbide respectively in high yield with absolute stereo control. Furthermore, by using this methodology dideoxy-amino isomannide-a tricyclic adduct-was obtained starting from isoidide in high yield. Our improved synthetic route is a valuable advance towards meeting scale and purity demands for evaluating the properties of new biobased performance materials, which will benefit the development of these plastics. PMID:22121062
Thiyagarajan, Shanmugam; Gootjes, Linda; Vogelzang, Willem; van Haveren, Jacco; Lutz, Martin; van Es, Daan S
Synthesis of a new polymeric host material for efficient organic electro-phosphorescent devices.
We have synthesized a new polymeric host material for phosphorescent dyes, which can be used in phosphorescent light-emitting layers. An alternating copolymer, composed of N-alkylcarbazole and tetramethylbenzene units was synthesized through the Suzuki coupling reaction. We fabricated electro-phosphorescent devices using the synthesized polymeric host doped with solution-processible green and red phosphorescent dyes. Light-emitting devices have an ITO/PEDOT/polymer + dopant/Balq3/Alq3/LiF/Al configuration. The device containing one of two studied green dopants (designated as green 1) in the polymeric host showed the best performance, with a maximum luminous efficiency of 29 cd/A. A thin film of this polymeric was successfully patterned by laser-induced thermal imaging (LITI), and an electro-phosphorescent device was fabricated using the patterned film. This patterned device showed performance characteristics similar to those of a spin-coated device. PMID:19049077
Hwang, Do-Hoon; Park, Moo-Jin; Eom, Jae-Hoon; Shim, Hong Ku; Lee, Seongtaek; Yang, Nam Ghoul; Lian, Duan; Suh, Min Chul; Chin, Byung Doo
Copper-catalyzed coupling of oxime acetates with sodium sulfinates: an efficient synthesis of sulfone derivatives.
Sulfone derivatives are important synthetic intermediates. However, the general method for their preparation is through traditional coupling reaction: the alkylation of sodium sulfinates with phenacyl halides. Based on our previous work on sodium sulfinates and oxime acetates, we herein report a novel method for sulfone derivatives by oxidative coupling with sodium sulfinates and oxime acetates using copper as catalyst. The sulfonylvinylamine products could be formed in excellent yields. Upon hydrolysis by silica gel in CH2 Cl2 , ?-ketosulfones could also be efficiently constructed. Various sulfonylvinylamines and ?-ketosulfones were obtained in good to excellent yields under the optimized reaction conditions. Mechanistic studies indicated that this transformation involved copper-catalyzed N-O bond cleavage, activation of a vinyl sp(2) C-H bond, and C-S bond formation. The oxime acetates act as both a substrate and an oxidant, thus the reaction needs no additional oxidants or additives. PMID:24677481
Tang, Xiaodong; Huang, Liangbin; Xu, Yanli; Yang, Jidan; Wu, Wanqing; Jiang, Huanfeng
Design synthesis and optimization of permanent magnet synchronous machines based on computationally-efficient finite element analysis
In this dissertation, a model-based multi-objective optimal design of permanent magnet ac machines, supplied by sine-wave current regulated drives, is developed and implemented. The design procedure uses an efficient electromagnetic finite element-based solver to accurately model nonlinear material properties and complex geometric shapes associated with magnetic circuit design. Application of an electromagnetic finite element-based solver allows for accurate computation of intricate performance parameters and characteristics. The first contribution of this dissertation is the development of a rapid computational method that allows accurate and efficient exploration of large multi-dimensional design spaces in search of optimum design(s). The computationally efficient finite element-based approach developed in this work provides a framework of tools that allow rapid analysis of synchronous electric machines operating under steady-state conditions. In the developed modeling approach, major steady-state performance parameters such as, winding flux linkages and voltages, average, cogging and ripple torques, stator core flux densities, core losses, efficiencies and saturated machine winding inductances, are calculated with minimum computational effort. In addition, the method includes means for rapid estimation of distributed stator forces and three-dimensional effects of stator and/or rotor skew on the performance of the machine. The second contribution of this dissertation is the development of the design synthesis and optimization method based on a differential evolution algorithm. The approach relies on the developed finite element-based modeling method for electromagnetic analysis and is able to tackle large-scale multi-objective design problems using modest computational resources. Overall, computational time savings of up to two orders of magnitude are achievable, when compared to current and prevalent state-of-the-art methods. These computational savings allow one to expand the optimization problem to achieve more complex and comprehensive design objectives. The method is used in the design process of several interior permanent magnet industrial motors. The presented case studies demonstrate that the developed finite element-based approach practically eliminates the need for using less accurate analytical and lumped parameter equivalent circuit models for electric machine design optimization. The design process and experimental validation of the case-study machines are detailed in the dissertation.
Sizov, Gennadi Y.
Efficient one-step synthesis of 4-amino substituted phthalimides and evaluation of their potential as fluorescent probes.
The phthalimide scaffold is recognized from bioactive compounds and marketed drugs, but can also be used as fluorescent probes by introducing a 4-amino substituent. Unfortunately, a general and convenient method to synthesize various 4-amino substituted phthalimides has been lacking. To overcome this, an atom efficient one-step synthesis of 4-amino substituted phthalimides in good to excellent yields that tolerate a wide range of substituents has been developed. Several of the generated compounds display interesting solvatochromic properties with high quantum yield of fluorescence in non-polar solvents that are significantly reduced in polar protic solvents. Many of these compounds displayed non-toxic properties and non-detectable unspecific binding and can thus potentially be linked to a substrate and used as fluorescent probes. Furthermore, bioactive and fluorescent 4-amino substituted phthalimides with IC50-values in the low micromolar range in cell-based assays have been identified and could be used to study uptake and distribution. The developed convenient synthetic method is thus valuable not only to construct fluorescent probes and fluorescent bioactive compounds to gain information about target binding, but also from a structure activity point of view in the various areas where the phthalimides have displayed activity. PMID:24849574
Kindahl, Tomas; Chorell, Erik
Synthesis efficiency of heavy carbon clusters from ETFE ablated by different numbers of laser pulse in vacuum
We have carried out mass spectral analysis of positive ions produced by laser ablation of a copolymer of ethylene and tetrafluoroethylene (ETFE: [?CH 2?CH 2?CF 2?CF 2?] n) in vacuum using time-of-flight mass spectrometry (TOF-MS). The surfaces of the ETFE targets irradiated by different numbers of laser pulse were analyzed by X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). Heavy carbon cluster ions C n+ with n?30 were observed in the mass spectra. The fractional abundance of heavy clusters in the mass spectrum decreased with the number of laser pulse. On the other hand, carbon became rich in the atomic composition of the laser-irradiated surface, and the eroded area on the surface increased with the number of laser pulse. From these results, it is suggested that the carbon-rich material surface results in the less efficient production of heavy carbon clusters. In addition, it is also suggested that clustering reactions in eroded craters do not contribute to the synthesis of heavy clusters.
Shibagaki, K.; Takada, N.; Sasaki, K.; Kadota, K.
Highly efficient synthesis of low polydispersity core cross-linked star polymers by Ru-catalyzed living radical polymerization.
The efficient formation of low polydispersity core cross-linked star (CCS) polymers via controlled/living radical polymerization (LRP) and the arm-first approach was found to be dependent on the mediating catalyst system. The Ru catalyst, Ru(Ind)Cl(PPh?)? Cat. 1, and tertiary amine co-catalyst were used to synthesize highly living poly(methyl methacrylate) (PMMA) macroinitiators, which were then linked together with ethylene glycol dimethacrylate (EGDMA) to form PMMA(arm)PEGDMA(core) CCS polymers. The quantitative and near-quantitative synthesis of CCS polymers were observed for low to moderate molecular weight macroinitiators (M(n) = ?8 and 20?kDa), respectively. Lower conversions were observed for high-molecular weight macroinitiators (M(n) ?? ?60?kDa). Overall, an improvement of between 10 and 20% was observed when comparing the Cat. 1 system to a conventional Cu-catalyzed system. This significant improvement in macroinitiator-to-star conversion is explained in the context of catalyst system selection and CCS polymer formation. PMID:21433199
Goh, Tor Kit; Yamashita, Satoshi; Satoh, Kotaro; Blencowe, Anton; Kamigaito, Masami; Qiao, Greg G
Regulation of 6S RNA by pRNA synthesis is required for efficient recovery from stationary phase in E. coli and B. subtilis
6S RNAs function through interaction with housekeeping forms of RNA polymerase holoenzyme (E?70 in Escherichia coli, E?A in Bacillus subtilis). Escherichia coli 6S RNA accumulates to high levels during stationary phase, and has been shown to be released from E?70 during exit from stationary phase by a process in which 6S RNA serves as a template for E?70 to generate product RNAs (pRNAs). Here, we demonstrate that not only does pRNA synthesis occur, but it is an important mechanism for regulation of 6S RNA function that is required for cells to exit stationary phase efficiently in both E. coli and B. subtilis. Bacillus subtilis has two 6S RNAs, 6S-1 and 6S-2. Intriguingly, 6S-2 RNA does not direct pRNA synthesis under physiological conditions and its non-release from E?A prevents efficient outgrowth in cells lacking 6S-1 RNA. The behavioral differences in the two B. subtilis RNAs clearly demonstrate that they act independently, revealing a higher than anticipated diversity in 6S RNA function globally. Overexpression of a pRNA-synthesis-defective 6S RNA in E. coli leads to decreased cell viability, suggesting pRNA synthesis-mediated regulation of 6S RNA function is important at other times of growth as well.
Cavanagh, Amy T.; Sperger, Jamie M.; Wassarman, Karen M.
Autographa californica multiple nucleopolyhedrovirus ac66 is required for the efficient egress of nucleocapsids from the nucleus, general synthesis of preoccluded virions and occlusion body formation.
Although orf66 (ac66) of Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is conserved in all sequenced lepidopteran baculovirus genomes, its function is not known. This paper describes generation of an ac66 knockout AcMNPV bacmid mutant and analyses of the influence of ac66 deletion on the virus replication in Sf-9 cells so as to determine the role of ac66 in the viral life cycle. Results indicated that budded virus (BV) yields were reduced over 99% in ac66-null mutant infected cells in comparison to that in wild-type virus infected cells. Optical microscopy revealed that occlusion body synthesis was significantly reduced in the ac66 knockout bacmid-transfected cells. In addition, ac66 deletion interrupted preoccluded virion synthesis. The mutant phenotype was rescued by an ac66 repair bacmid. On the other hand, real-time PCR analysis indicated that ac66 deletion did not affect the levels of viral DNA replication. Electron microscopy revealed that ac66 is not essential for nucleocapsid assembly, but for the efficient transport of nucleocapsids from the nucleus to the cytoplasm. These results suggested that ac66 plays an important role for the efficient exit of nucleocapsids from the nucleus to the cytoplasm for BV synthesis as well as for preoccluded virion and occlusion synthesis. PMID:18241908
Ke, Jianhao; Wang, Jinwen; Deng, Riqiang; Wang, Xunzhang
Synthesis of Efficiently Green Luminescent CdSe/ZnS Nanocrystals Via Microfluidic Reaction
Quantum dots with emission in the spectral region from 525 to 535 nm are of special interest for their application in green LEDs and white-light generation, where CdSe/ZnS core-shell structured nanocrystals (NCs) are among promising candidates. In this study, triple-ligand system (trioctylphosphine oxide�oleic acid�oleylamine) was designed to improve the stability of CdSe NCs during the early reaction stage. With the precisely controlled reaction temperature (285 �C) and residence time (10 s) by the recently introduced microfluidic reaction technology, green luminescent CdSe NCs (? = 522 nm) exhibiting narrow FWHM of PL (30 nm) was reproducibly obtained. After that, CdSe/ZnS core-shell NCs were achieved with efficient luminescence in the pure green spectral region, which demonstrated high PL QY up to 70% and narrow PL FWHM as 30 nm. The strengthened mass and heat transfer in the microchannel allowed the formation of highly luminescent CdSe/ZnS NCs under low reaction temperature and short residence time (T = 120 �C,t = 10 s). The successful formation of ZnS layer was evidence of the substantial improvement of PL intensity, being further confirmed by XRD, HRTEM, and EDS study.
Synthesis of carbon black/carbon nitride intercalation compound composite for efficient hydrogen production.
The photoactivity of g-C3N4 is greatly limited by its high recombination rate of photogenerated carriers. Coupling g-C3N4 with other materials has been demonstrated to be an effective way to facilitate the separation and transport of charge carriers. Herein we report a composite of conductive carbon black and carbon nitride intercalation compound synthesized through facile one-step molten salt method. The as-prepared carbon black/carbon nitride intercalation compound composite was characterized by X-ray diffraction (XRD) and transmission electron microscopy (TEM), UV-vis absorption spectrum and photoluminescence spectroscopy (PL). The carbon black nanoparticles, homogeneously dispersed on the surface of carbon nitride intercalation compound, efficiently enhanced separation and transport of photogenerated carriers, thus improving the visible-light photocatalytic activity. The composite of 0.5 wt% carbon black and carbon nitride intercalation compound exhibited a H2 production rate of 68.9 ?mol h(-1), which is about 3.2 times higher than hydrogen production on pristine carbon nitride intercalation compound. PMID:24975427
Wu, Zhaochun; Gao, Honglin; Yan, Shicheng; Zou, Zhigang
Synthesis, spectral, SHG efficiency and computational studies of some newly synthesized unsymmetrical azines of 4-biphenylcarboxaldehyde
A series of novel unsymmetrical azines 2-8 are prepared and characterized by FT-IR, 1H, 13C NMR, Mass and UV spectral studies. The Gaussian-03 B3LYP/6-311+G(d,p) calculations on these azines are used to evaluate the heat of formation of the different conformers, identify the stable conformation, to determine dipole moment (?), polarizability (?0), first hyperpolarizability (?tot), selected geometrical parameters, MEP surface, frontier molecular orbital energies (HOMO-LUMO) and their energy gap. The ?, ?0, ?tot values clearly depict that the unsymmetrical azine 8 is found to have a good NLO property compared to other azines 1-7. The SHG measurement of unsymmetrical azine 8 was performed by Kurtz and Perry powder method and the results indicated that the azine 8 is having comparable efficiency as that of potassium dihydrogen phosphate (KDP) crystal. The natural bond orbital (NBO) analysis of the unsymmetrical azines 2-8 are also made using B3LYP/6-31G(d,p) basis set.
Arulmani, R.; Sankaran, K. R.
Synthesis of copper hydroxide and oxide nanostructures via anodization technique for efficient photocatalytic application.
We have demonstrated a facile protocol for synthesizing CuO and Cu2O mixed-phase nanostructures by anodization of copper hydroxide (Cu(OH)2) nanoneedles and their heat treatment in different atmospheres, which affect photocatalytic degradation efficiency. The oxygen annealed sample had relatively small (100 nm) lamellar, spherical nanoparticulate structures on the substrate surface, which showed better photocatalytic degradation of reactive black 5 dye resulting from the appropriate morphology and phase formation, compared to the samples annealed in different atmospheres and vacuum. The pseudo first-order rate constant (k) of the oxygen annealed sample was 0.0054/min, which was relatively high due to the formation of a CuO-Cu2O heterojunction with matching band potentials. Air, nitrogen, argon and vacuum annealing resulted in bigger particles and different morphologies, which led to pseudo first-order rate constants (k) of 0.0032/min (air-annealed); 0.0021/min (N2-annealed); 0.0033/min (Ar-annealed); and 0.0027/min (vacuum-annealed), which resulted in poor photocatalytic degradation of the reactive black 5 dye. PMID:23421221
Hyam, Rajeshkumar Shankar; Lee, Jongseok; Cho, Eunju; Khim, Jeehyeong; Lee, Haigun
Synthesis of novel chitosan-silica/CpG oligodeoxynucleotide nanohybrids with enhanced delivery efficiency.
Chitosan-silica/CpG oligodeoxynucleotide (ODN) nanohybrids were synthesized to stimulate Toll-like receptor 9-mediated induction of interleukin-6 (IL-6). The chitosan-silica hybrid was first synthesized from a mixture of chitosan and 3-glycidoxypropyl trimethoxysilane under acidic conditions via a sol-gel process, and then used to condense CpG ODN2006x3-PD to yield chitosan-silica/CpG ODN nanohybrids. Scanning electron microscopy and atomic force microscopy showed that the chitosan-silica/CpG ODN nanohybrids had an elliptic shape with a diameter of 100-200 nm. After soaking in HAc-NaAc buffer solution (pH5.5), the nanohybrids exhibited sustained release of CpG ODN. When the nanohybrids were separately exposed to 293XL-hTLR9 cells and peripheral blood mononuclear cells, no significant toxicity was observed. An immunochemical assay for cellular uptake revealed that the nanohybrids were taken up by the cells and located in endolysosomes. An enzyme-linked immunosorbent assay for cytokines indicated that the nanohybrids effectively stimulated the induction of IL-6. Chitosan-silica/CpG ODN nanohybrids underwent cellular uptake and enhanced induction of IL-6 to a greater degree than conventional chitosan/CpG ODN nanocomplexes, indicating that they have an enhanced delivery efficiency. PMID:23706224
Chen, Song; Zhang, Huijie; Chinnathambi, Shanmugavel; Hanagata, Nobutaka
Synthesis, structural characterisation, bio-potential efficiency and DNA cleavage applications of nicotinamide metal complexes
Mixed ligand complexes were synthesised using nicotinamide as the primary ligand and nitrite as the secondary ligand were characterised by FT-IR, UV-Vis, 1H NMR, TG-DTA-DTG, X-ray powder diffraction and physical analytical studies. From the molar conductance, magnetic moment and electronic spectral data of the synthesised complexes a general formula of [M(ONO)2(NA)2] where M = Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II) and [Cr2(ONO)6(NA)2] with a distorted octahedral structure were proposed. Thermal analyses show that the complexes lose molecules of hydration initially and subsequently expel anionic and organic ligands in continuous steps. The kinetic parameter values, such as, E*, ?H*, ?S* and ?G* illustrate the spontaneous association of the metal and ligands in the formation of the complexes. The antimicrobial efficacy of the ligand and its complexes were examined by in vitro method against various pathogenic bacterial and fungal strains. The metal complexes were found to posses efficient antimicrobial properties compared to nicotinamide and a few of these complexes could turn out to be excellent models for the design of effective antibiotic drug substances. The intercalating interaction of Cu(II) complex with CT-DNA was inspected by absorption spectral and viscosity studies, thermal denaturation and electro-analytical experiments.
Surendra Dilip, C.; Siva Kumar, V.; John Venison, S.; Vetha potheher, I.; Rajalaxmi (a) Subahashini, D.
Synthesis and characterization of wafer-like BiFeO 3 with efficient catalytic activity
Wafer-like paramagnetic BiFeO 3 were successfully fabricated via hydrothermal route without any dispersant or mineralizer. The obtained samples exhibited a rhombohedral single-phase and a narrow band gap of 2.05 eV. Its catalytic activity was investigated and it was found that the degradation efficiency of 10 mg L -1 Rhodamine B was above 90.5% over 1.0 g L -1 BiFeO 3 within 10 mmol L -1 H 2O 2 at pH 5.7 and temperature 25 �C in 3 h under the visible-light irradiation. It was revealed that BiFeO 3 possessed excellent reusability. The modified electrode of synthesized BiFeO 3-chitosan-glassy carbon electrode could dramatically enhance the peak current in 1 mM K 3[Fe(CN) 6]/K 4[Fe(CN) 6] solution, suggesting its potential application in electrochemical analysis.
Jiang, Jizhou; Zou, Jing; Anjum, Muhammad Naveed; Yan, Jingchun; Huang, Lei; Zhang, Yuanxiao; Chen, Jinfang
Synthesis, spectral, SHG efficiency and computational studies of some newly synthesized unsymmetrical azines of 4-biphenylcarboxaldehyde.
A series of novel unsymmetrical azines 2-8 are prepared and characterized by FT-IR, (1)H, (13)C NMR, Mass and UV spectral studies. The Gaussian-03 B3LYP/6-311+G(d,p) calculations on these azines are used to evaluate the heat of formation of the different conformers, identify the stable conformation, to determine dipole moment (?), polarizability (?0), first hyperpolarizability (?tot), selected geometrical parameters, MEP surface, frontier molecular orbital energies (HOMO-LUMO) and their energy gap. The ?, ?0, ?tot values clearly depict that the unsymmetrical azine 8 is found to have a good NLO property compared to other azines 1-7. The SHG measurement of unsymmetrical azine 8 was performed by Kurtz and Perry powder method and the results indicated that the azine 8 is having comparable efficiency as that of potassium dihydrogen phosphate (KDP) crystal. The natural bond orbital (NBO) analysis of the unsymmetrical azines 2-8 are also made using B3LYP/6-31G(d,p) basis set. PMID:24755639
Arulmani, R; Sankaran, K R
Synthesis and characterization of chitosan tripolyphosphate nanoparticles and its encapsulation efficiency containing Russell's viper snake venom.
Chitosan Tripolyphosphate (CS/TPP) nanoparticle is a biodegradable and nontoxic polysaccharide, used as a carrier for drug delivery. The morphology and particle-size measurements of the nanoparticles were studied by field emission scanning electron microscopy and Fourier Transform Infrared Spectroscopy (FTIR). This study aims to evaluate the impact of Russell's viper venom encapsulation on various factors and loading capacity, in addition to explore the physicochemical structure of nanoparticles. FTIR confirmed that tripolyphosphoric groups of TPP linked with ammonium groups of CS in the nanoparticles. Our results showed that CS can react with TPP to form stable cationic nanoparticles. The results also showed that encapsulation efficiency of venom at different concentrations of 20, 40, 60, 500, and 1000 �g/mL were achieved for CS/TPP nanoparticles at different concentrations of 1.5, 2, and 3 mg/mL. The cytotoxicity of CS/TPP nanoparticles was evaluated by MTT (-3 (4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, a tetrazole) assay. PMID:23712553
Venkatesan, C; Vimal, S; Hameed, A S Sahul
Reaction mechanism and chemoselectivity of intermolecular cycloaddition reactions between phenyl-substituted cyclopropenone ketal and methyl vinyl ketone.
In this paper, the mechanisms of the intermolecular [3+2] and [1+2] cycloaddition reactions of 1,1/1,3-dipolar ?-delocalized singlet vinylcarbenes, which is obtained from cyclopropenone, with an electron-deficient C?O or C?C dipolarophile, to generate five-membered ring products are first disclosed by the density functional theory (DFT). Four reaction pathways, including two concerted [3+2] cycloaddition reaction pathways and two stepwise reaction pathways (an initial [1+2] cycloaddition and then a rearrangement from the [1+2] cycloadducts to the final [3+2] cycloadducts), are investigated at the B3LYP/6-31G(d,p) level of theory. The calculated results reveal that, in contrast to the concerted C?O [3+2] cycloaddition reaction pathway, which is 7.1 kcal/mol more energetically preferred compared with its stepwise reaction pathway, the C?C dipolarophile favors undergoing [1+2] cycloaddition rather than concerted [3+2] cycloaddition (difference of 5.3 kcal/mol). The lowest free energy barrier of the C?O concerted [3+2] cycloaddition reaction pathway shows that it predominates all other reaction pathways. This observation is consistent with the finding that the C?O [3 + 2] cycloadduct is the main product under experimental conditions. In addition, natural bond orbital second-order perturbation charge analyses are carried out to explain the preferred chemoselectivity of C?O to the C?C dipolarophile and the origins of cis-stereoselectivity for C?C [1+2] cycloaddition. Solvent effects are further considered at the B3LYP/6-31G(d,p) level in the solvents CH(3)CN, DMF, THF, CH(2)Cl(2), toluene, and benzene using the PCM model. The results indicate that the relative reaction trends and the main products are insensitive to the polarity of the reaction solvent. PMID:21438618
Qiao, Yan; Chu, Tian-Shu
Amberlyst-15: An efficient reusable heterogeneous catalyst for the synthesis of 1,8-dioxo-octahydroxanthenes and 1,8-dioxo-decahydroacridines
Amberlyst-15 has been found to be an efficient catalyst for the synthesis of 1,8-dioxo-octahydroxanthenes and 1,8-dioxo-decahydroacridines in excellent yields. The former have been synthesized from aromatic aldehydes and 5,5-dimethyl-1,3-cyclohexanedione while the latter from this mixture along with amines. The method is an easy access to functionalized xanthene and acridine derivatives. The catalyst can be reused.
Biswanath Das; Ponnaboina Thirupathi; I. Mahender; V. Saidi Reddy; Yerra Koteswara Rao
ONE-POT SYNTHESIS OF 2,4,5TRISUBSTITUTED IMIDAZOLES USING [BPy]H2PO4, AN EFFICIENT AND RECYCLABLE CATALYST
[BPy]H2PO4 was easily prepared and used as efficient and recyclable catalyst for the one-pot synthesis of 2,4,5-trisubstituted imidazoles under solvent-free conditions in good to excellent yields. Solvent-free conditions, simple experimental and work-up procedures, along with the use of non-toxic, recyclable catalyst of an environmentally benign nature are remarkable features of the procedure.
Yuliang Zhang; Zhongqiang Zhou
Efficient one-pot multienzyme synthesis of UDP-sugars using a promiscuous UDP-sugar pyrophosphorylase from Bifidobacterium longum (BLUSP).
A promiscuous UDP-sugar pyrophosphorylase (BLUSP) was cloned from Bifidobacterium longum strain ATCC55813 and used efficiently with a Pasteurella multocida inorganic pyrophosphatase (PmPpA) with or without a monosaccharide 1-kinase for one-pot multienzyme synthesis of UDP-galactose, UDP-glucose, UDP-mannose, and their derivatives. Further chemical diversification of a UDP-mannose derivative resulted in the formation of UDP-N-acetylmannosamine. PMID:22306833
Muthana, Musleh M; Qu, Jingyao; Li, Yanhong; Zhang, Lei; Yu, Hai; Ding, Li; Malekan, Hamed; Chen, Xi
Population Synthesis Studies of Close Binary Systems Using a Variable Common Envelope Efficiency Parameter. I. Dependence on Secondary Mass
We perform population synthesis calculations of present-day post-CE binaries (PCEBs) and zero-age cataclysmic variables (ZACVs) using a common envelope (CE) efficiency parameter, ?CE, that is a function of secondary mass, Ms. We investigate three basic possibilities: (1) a standard constant ?CE prescription, with ?CE ranging from 0.05 to 1.0, to provide a baseline for comparison; (2) a power-law dependence, ?CE=(Ms)n, with n=0.5, 1.0, and 2.0; and (3) a dependence in which ?CE approaches 1 for large Ms and ?CE=0 below some assumed cutoff mass, ?CE=1-Mcut/Ms, where Mcut=0.0375, 0.075, and 0.15 Msolar. We find that if ?CE<~0.2 in our constant ?CE sequence, the predicted present-day ZACV population is significantly modified compared with our standard model (?CE=1.0). All prior population synthesis calculations of the formation of CVs only considered values of ?CE>=0.3 and found that their model populations were not strongly dependent upon the value of ?CE. Our results indicate that a much wider range of values for ?CE, including very low values, must be considered in order for a dependence to be seen. In our variable ?CE sequences for ZACVs, we find that for models in which ?CE decreases very rapidly for small Ms, the orbital period distribution below the period gap differs significantly from our standard model. In particular, the fraction of CVs forming with P<2 hr is reduced significantly, the fraction forming in the gap is increased significantly, and both the short-period peak and the minimum period shift to considerably longer periods compared with our standard model. We suggest that the observed scarcity of CVs with P<77 minutes may possibly provide evidence that progenitor binaries with Ms<~0.10 Msolar are unable to avoid merger within the CE. We also suggest that if ?CE decreases rapidly for small Ms, it is possible that the lower edge of the period gap could be, in part, an imprint of the ZACV population.
Politano, Michael; Weiler, Kevin P.
Adenovirus type 5 early region 1b gene product is required for efficient shutoff of host protein synthesis.
To determine the role adenovirus 5 early region 1b-encoded 21- and 55-kilodalton proteins play in adenovirus productive infection, mutants have been isolated which were engineered to contain small deletions or insertions at 5.8, 7.9, or 9.6 map units. By using an overlap recombination procedure involving H5dl314 (delta 3.7 to 4.6 map units) DNA cleaved at 2.6 map units with ClaI and the adenovirus 5 XhoI-C (0 to 15.5 map units) fragment containing the desired mutation, viral mutants were isolated by their ability to produce plaques on KB cell line 18, which constitutively expresses only viral early region 1b functions (Babiss et al., J. Virol. 46:454-465, 1983). DNA sequence analysis of the viral mutants isolated (H5dl118, H5dl110, H5in127, and H5dl163) indicates that all of the viruses contain mutations which affect the 55-kilodalton protein, whereas dl118 should also produce a truncated form of the 21-kilodalton protein. When analyzed for their replication characteristics in HeLa cells, all of the mutant viruses exhibited extended eclipse periods and effected yields that were reduced to 10% or less of that produced by H5sub309 (parent virus of the mutants which is phenotypically identical to wild-type adenovirus 5). When compared with characteristics of sub309, the early and late transcription and DNA replication of the mutants were similar, but synthesis of late polypeptides and late cytoplasmic mRNAs was greatly reduced. Quantitation of mutant virus-specific late mRNAs associated with polysomes revealed a threefold reduction when compared with that of sub309. Analysis of infected cell extracts further revealed that these mutants were incapable of efficiently shutting off host cell protein synthesis, suggesting that the 55-kilodalton protein plays a role in this process. These data suggest that early region 1b products may function by interacting with additional viral or host cell macromolecules to modulate host cell shutoff or that some late viral mRNA or polypeptide may potentiate this reaction. Images
Babiss, L E; Ginsberg, H S
Synthesis of glycal-based chiral benzimidazoles by VO(acac)2-CeCl3 combo catalyst and their self-aggregated nanostructured materials.
VO(acac)(2)-CeCl(3) combo catalyst has been developed for chemoselective cyclocondensation cum oxidation under mild reaction conditions toward synthesis of a new class of optically pure compounds, 2-(2'-C-3',4',6'-tri-O-benzyl/methyl-glycal)-1H-benzimidazoles. It involves an operationally simple synthetic protocol efficient for the syntheses of a wide range of chiral benzimidazoles in high yields without formation of undesired 1,2-disubstituted and pseudoglycal byproducts. Vanadium(V) is found as active oxidant for the chemical processes which is investigated by UV absorption spectroscopy. Highly ordered one-dimensional low molecular mass organic nanostructured materials are fabricated by nanocrystallization of the chiral nanoscale building blocks. Theoretical calculation by the B3LYP/6-31G** level of theory of the glycal-based chiral benzimidazoles shows out of planar geometry of the 1H-anthra[1,2-d]imidazole-6,11-dione moiety, which is responsible for the strong self-aggregation to generate ultralong nanostructured materials. We have also found nice agreement between the theoretical results with the experimental observation in 2D-NOESY experiments. The photophysical property of the solid nanostructured materials is also reported. PMID:19799443
Maiti, Dilip K; Halder, Samiran; Pandit, Palash; Chatterjee, Nirbhik; De Joarder, Dripta; Pramanik, Nabyendu; Saima, Yasmin; Patra, Amarendra; Maiti, Prabir K
Rational design and synthesis of efficient Carbon and/or Silica functional nanomaterials for electrocatalysis and nanomedicine
In nanomaterials there is a strong correlation between structure and properties. Thus, the design and synthesis of nanomaterials with well-defined structures and morphology is essential in order to produce materials with not only unique but also tailorable properties. The unique properties of nanomaterials in turn can be taken advantage of to create materials and nanoscale devices that can help address important societal issues, such as meeting renewable energy sources and efficient therapeutic and diagnostic methods to cure a range of diseases. In this thesis, the different synthetic approaches I have developed to produce functional nanomaterials composed of earth-abundant elements (mainly carbon and silica) at low cost in a very sustainable manner are discussed. In Chapter 1, the fundamental properties of nanomaterials and their properties and potential applications in many areas are introduced. In chapter 2, a novel synthetic method that allows polymerization of polyaniline (PANI), a conducting polymer, inside cylindrical channel pores of nanoporous silica (SBA-15) is discussed. In addition, the properties of the III resulting conducting polymer in the confined nanochannel spaces of SBA-15, and more importantly, experimental demonstration of the use of the resulting hybrid material (PANI/SBA-15 material) as electocatalyst for electrooxidation reactions with good overpotential, close to zero, are detailed. In chapter 3, the synthetic approach discussed in Chapter 2 is further extended to afford nitrogen- and oxygen-doped mesoporous carbons. This is possible by pyrolysis of the PANI/SBA-15 composite materials under inert atmosphere, followed by etching away their silica framework. The high catalytic activity of resulting carbon-based materials towards oxygen reduction reaction despite they do not possess any metal dopants is also included. The potential uses of nanomaterials in areas such as nanomedicine need deep understanding of the biocompatibility/ toxicity of the materials. In Chapter 4, comparative in vitro and in vivo assessments of the biological properties and murine lung toxicity (biocompatibility) of the carbon-based nanomaterials synthesized above and in core-shell architectures containing carbon, silica and cobalt is presented. The results indicate that silica shell is essential for biocompatibility. Furthermore, cobalt oxide is the preferred phase over the zero valent Co(0) phase to impart biocompatibility to cobalt-based nanoparticles. This study is a result of collaboration between Asefa's research group at Rutgers University and Souid's research group at United Arab Emirates University. In Chapter 5, a new synthetic method to carbon nanoneedles (or a new class of carbon nanomaterials with high aspect ratios) is presented. In the work, cellulose nanocrystals are prepared and used as precursor for carbon nanostructures. Unlike other types of carbon nanomaterials, carbon IV nanoneedles possess high surface area and large proportion of edge planes, which have outstanding charge transfer and catalytic properties. The resulting metal-free, carbon nanoneedles are shown to serve as effective electrocatalysts for oxidation of hydrazine. In Chapter 6, the synthesis of amorphous carbon nanoneedles containing cobalt and their catalytic activities for oxygen reduction reaction is discussed. Even though the activity of the materials is lower than the one discussed in Chapter 3 for polyaniline-derived mesoporous carbons, the result and discussion in this chapter provides new insights on the effects and advantages of carbon nanoneedles on the electrocatalytic activity of the materials. In addition, the effects of cobalt content and nanoneedles' structures on the catalytic activity of the materials are described. In chapter 7, the synthesis of very small Au nanoparticles within SBA-15 mesoporous silica host materials by galvanic exchange reactions is described. The resulting Au/SBA-15 materials with different size Au nanoparticles are shown to have very interesting surface plasmon resonance (SPR) activity as a result of
Da Silva, Rafael
An Efficient Synthesis of de novo Imidates via Aza-Claisen Rearrangements of N-Allyl Ynamides
A novel thermal 3-aza-Claisen rearrangement of N-allyl ynamides for the synthesis of ?-allyl imidates is described. Also, a sequential aza-Claisen, Pd-catalyzed Overman rearrangement is described for the synthesis of azapine-2-ones.
DeKorver, Kyle A.; North, Troy D.; Hsung, Richard P.
Witting Reaction Using a Stabilized Phosphorus Ylid: An Efficient and Stereoselective Synthesis of Ethyl Trans-Cinnamate
An instructive experiment for the synthesis of ethyl trans-cinnamate, a pleasant smelling ester used in perfumery and flavoring by the reaction of benzaldehyde with the stable ylid triphenylphosphorane is described. The synthesis, workup and characterization of trans-cinnamate may be accomplished in a single laboratory session with commonly�
Speed, Traci J.; Mclntyre, Jean P.; Thamattoor, Dasan M.
Trifluoroacetic Acid as an Efficient Catalyst for One-Pot, Four-Component Synthesis of 1,2,4,5Tetrasubstituted Imidazoles Under Microwave-Assisted, Solvent-Free Conditions
An efficient method for synthesis of various tetrasubstituted imidazoles, using trifluoroacetic acid (TFA) as a catalytic support, by four-component condensation of benzil, aldehydes, amines, and ammonium acetate under microwave-irradiated, solvent-free conditions is described.
Mohammad R. Mohammadizadeh; Alireza Hasaninejad; M. Bahramzadeh
Chemoselective C-4 aerobic oxidation of catechin derivatives catalyzed by the Trametes villosa laccase/1-hydroxybenzotriazole system: synthetic and mechanistic aspects.
Catechin derivatives were oxidized in air in the presence of the Trametes villosa laccase/1-hydroxybenzotriazole (HBT) system in buffered water/1,4-dioxane as reaction medium. The oxidation products, flavan-3,4-diols and the corresponding C-4 ketones, are bioactive compounds and useful intermediates for the hemisynthesis of proanthocyanidins, plant polyphenols which provide beneficial health properties for humans. Determinations of oxidation potentials excluded that catechin derivatives could be directly oxidized by laccase Cu(II), while it resulted in the H-abstraction from benzylic positions being promptly promoted by the enzyme in the presence of the mediator HBT, the parent species producing in situ the reactive intermediate benzotriazole-N-oxyl (BTNO) radical. A remarkable and unexpected result for the laccase/HBT oxidative system has been the chemoselective insertion of the oxygen atom into the C-4-H bond of catechin derivatives. Mechanistic aspects of the oxidation reaction have been investigated in detail for the first time in order to corroborate these results. Since the collected experimental findings could not alone provide information useful to clarify the origin of the observed chemoselectivity, these data were expressly supplemented with information derived by suitable molecular modeling investigations. The integrated evaluation of the dissociation energies of the C-H bonds calculated both by semiempirical and DFT methods and the differential activation energies of the process estimated by a molecular modeling approach suggested that the observed selective oxidation at the C-4 carbon has a kinetic origin. PMID:21204551
Bernini, Roberta; Crisante, Fernanda; Gentili, Patrizia; Morana, Fabio; Pierini, Marco; Piras, Monica
Organic-inorganic hybrid supermicroporous iron(III) phosphonate nanoparticles as an efficient catalyst for the synthesis of biofuels.
Here we report a novel family of crystalline, supermicroporous iron(III) phosphonate nanomaterials (HFeP-1-3, HFeP-1-2, and HFeP-1-4) with different Fe(III)-to-organophosphonate ligand mole ratios. The materials were synthesized by using a hydrothermal reaction between benzene-1,3,5-triphosphonic acid and iron(III) chloride under acidic conditions (pH ? 4.0). Powder X-ray diffraction, N2 sorption, transmission and scanning electron microscopy (TEM and SEM) image analysis, thermogravimetric and differential thermal analysis (TGA-DTA), and FTIR spectroscopic tools were used to characterize the materials. The triclinic crystal phase [P1(2) space group] of the hybrid iron phosphonate was established by a Rietveld refinement of the PXRD analysis of HFeP-1-3 by using the MAUD program. The unit cell parameters are a = 8.749(1), b = 8.578(1), c = 17.725(3)?�; ? = 104.47(3), ? = 97.64(1), ? = 113.56(3)�; and V = 1013.41?�(3). With these crystal parameters, we proposed an 24-membered-ring open framework structure for HFeP-1. Compound HFeP-1-3, with an starting Fe/ligand molar ratio of 3.0, shows the highest Brunauer-Emmett-Telller (BET) surface area of 556?m(2) g(-1) and uniform supermicropores of approximately 1.1?nm. The acidic surface of the porous iron(III) phosphonate nanoparticles was used in a highly efficient and recyclable catalytic transesterification reaction for the synthesis of biofuels under mild reaction conditions. PMID:23650095
Pramanik, Malay; Bhaumik, Asim
Photocatalytic chemoselective reduction of epoxides to alkenes along with formation of ketones in alcoholic suspensions of silver-loaded titanium(iv) oxide at room temperature without the use of reducing gases.
(2,3-Epoxypropyl)benzene was chemoselectively reduced to allylbenzene along with formation of ketones in alcoholic suspensions of a silver-loaded titanium(iv) oxide photocatalyst at room temperature under atmospheric pressure without the use of reducing gases, and various epoxides were also reduced to the corresponding alkenes. PMID:24668000
Kominami, Hiroshi; Yamamoto, Satoshi; Imamura, Kazuya; Tanaka, Atsuhiro; Hashimoto, Keiji
Rapid Chemoselective Bioconjugation Through the Oxidative Coupling of Anilines and Aminophenols
A highly efficient protein bioconjugation method is described involving the addition of anilines to o-aminophenols in the presence of sodium periodate. The reaction takes place in aqueous buffer at pH 6.5 and can reach high levels of completion in 2�5 min. The product of the reaction has been characterized using X-ray crystallography, which revealed that an unprecedented oxidative ring contraction occurs after the coupling step. The compatibility of the reaction with protein substrates has been demonstrated through the attachment of small molecules, polymer chains, and peptides to p-aminophenylalanine residues introduced into viral capsids through amber stop codon suppression. The coupling of anilines to o-aminophenol groups derived from tyrosine residues is also described. The compatibility of this method with thiol modification chemistry is shown through the attachment of a near-IR fluorescent chromophore to cysteine residues inside the viral capsid shells, followed by the attachment of integrin-targeting RGD peptides to anilines on the exterior surface.
Behrens, Christopher R.; Hooker, Jacob M.; Obermeyer, Allie C.; Romanini, Dante W.; Katz, Elan M.; Francis, Matthew B.
Novel, fast and efficient one-pot sonochemical synthesis of 2-aryl-1,3,4-oxadiazoles.
Ultrasound promoted synthesis of 2-aryl-1,3,4-oxadiazoles at ambient temperature is reported. The remarkable features of the new procedure are shorter reaction time, excellent yields, cleaner reaction profile and simple experimental and workup procedure. PMID:23845411
Rouhani, Morteza; Ramazani, Ali; Joo, Sang Woo
Reactions of resin-bound triazenes with dithianylium tetrafluoroborates: efficient synthesis of ?-azo ketene dithioacetals and related hydrazones.
The conversion of dithianylium cations into ?-azo ketene dithioacetals via addition of polymer-bound diazonium precursors is shown. This new procedure allows the synthesis of ?-azo ketene dithioacetals in one step within 2-90 min at rt and yields highly pure compounds that do not have to be purified in most cases. The ?-azo ketene dithioacetals obtained have been shown to be valuable intermediates for the synthesis of hydrazones, ?-halogenated ?-azo ketene dithioacetals, and azo-functionalized dienes. PMID:24517451
Jung, Nicole; Stanek, Bettina; Gr��le, Simone; Nieger, Martin; Br�se, Stefan
Further studies on ethyl 5-hydroxy-indole-3-carboxylate scaffold: Design, synthesis and evaluation of 2-phenylthiomethyl-indole derivatives as efficient inhibitors of human 5-lipoxygenase.
5-Lipoxygenase (5-LO), an enzyme that catalyzes the initial steps in the biosynthesis of pro-inflammatory leukotrienes, is an attractive drug target for the pharmacotherapy of inflammatory and allergic diseases. Here, we present the design, synthesis and biological evaluation of novel series of ethyl 5-hydroxyindole-3-carboxylate derivatives that efficiently inhibit human 5-LO. SAR analysis revealed that the potency of compounds is closely related to the positioning of the substituents at the phenylthiomethyl ring. The introduction of methyl or chlorine groups in ortho- and ortho/para-position of thiophenol represent the most favorable modifications. Among all tested compounds, ethyl 5-hydroxy-2-(mesitylthiomethyl)-1-methyl-1H-indole-3-carboxylate (19) is the most potent derivative which blocks 5-LO activity in cell-free assays with IC50�=�0.7�?M, and suppressed 5-LO product synthesis in polymorphonuclear leukocytes with IC50�=�0.23�?M. PMID:24871899
Peduto, Antonella; Bruno, Ferdinando; Dehm, Friedrike; Krauth, Verena; de Caprariis, Paolo; Weinigel, Christina; Barz, Dagmar; Massa, Antonio; De Rosa, Mario; Werz, Oliver; Filosa, Rosanna
ZnO nanoparticles as an efficient, heterogeneous, reusable, and ecofriendly catalyst for four-component one-pot green synthesis of pyranopyrazole derivatives in water.
An extremely efficient catalytic protocol for the synthesis of a series of pyranopyrazole derivatives developed in a one-pot four-component approach in the presence of ZnO nanoparticles as heterogeneous catalyst using water as a green solvent is reported. Greenness of the process is well instituted as water is exploited both as reaction media and medium for synthesis of catalyst. The ZnO nanoparticles exhibited excellent catalytic activity, and the proposed methodology is capable of providing the desired products in good yield (85-90%) and short reaction time. After reaction course, ZnO nanoparticles can be recycled and reused without any apparent loss of activity which makes this process cost effective and hence ecofriendly. All the synthesized compounds have been characterized on the basis of elemental analysis, IR, �H NMR, and ��C NMR spectral studies. PMID:24282386
Sachdeva, Harshita; Saroj, Rekha
ZnO Nanoparticles as an Efficient, Heterogeneous, Reusable, and Ecofriendly Catalyst for Four-Component One-Pot Green Synthesis of Pyranopyrazole Derivatives in Water
An extremely efficient catalytic protocol for the synthesis of a series of pyranopyrazole derivatives developed in a one-pot four-component approach in the presence of ZnO nanoparticles as heterogeneous catalyst using water as a green solvent is reported. Greenness of the process is well instituted as water is exploited both as reaction media and medium for synthesis of catalyst. The ZnO nanoparticles exhibited excellent catalytic activity, and the proposed methodology is capable of providing the desired products in good yield (85�90%) and short reaction time. After reaction course, ZnO nanoparticles can be recycled and reused without any apparent loss of activity which makes this process cost effective and hence ecofriendly. All the synthesized compounds have been characterized on the basis of elemental analysis, IR, 1H NMR, and 13C NMR spectral studies.
A Bidirectional SE' Strategy for 1,5-syn and 1,5-anti Stereocontrol Toward the Synthesis of Complex Polyols
Studies report a bidirectional SE' strategy applicable for the stereocontrolled synthesis of nonracemic 1,5-syn and 1,5-anti diols and their derivatives. Nonracemic 1,3,2-diazaborolidine auxiliaries are incorporated by chemoselective tin�boron exchange to provide reactive allylic boranes. The convergent pathway utilizes sequential reactions with two aldehydes producing stereochemical outcomes from cyclic, closed and open transition state preferences, respectively. Synthesis of fragment 16 of peloruside A is accomplished in four steps from readily available aldehydes 9 and 13.
Williams, David R.; Claeboe, Christopher D.; Liang, Bo; Zorn, Nicolas; Chow, Nicholas S. C.
Stimuli-responsive hydrogel hollow capsules by material efficient and robust cross-linking-precipitation synthesis revisited.
Monodisperse stimuli-responsive hydrogel capsules were synthesized in the 100-nm-diameter to 10-?m-diameter range from poly(4-vinylpyridine) (P4VP) and poly(ethyleneimine) (PEI) through a simple, efficient two-step cross-linking-precipitation template method under conditions of a good solvent. In this method, the core-shell particles were obtained by the deposition (heterocoagulation mechanism) of the cross-linked P4VP, PEI, or their mixtures on the surfaces of the template colloidal silica particles in nitromethane (for PEI) or a nitromethane-acetone mixture (for P4VP and P4VP-PEI mixtures) in the presence of cross-linker 1,4-diiodobutane. The cross-linked polymeric shell swollen in a good solvent stabilized the core-shell colloids. This mechanism provided the conditions for the synthesis of core-shell colloids in a submicrometer range of dimensions with an easily adjusted shell thickness (wall of the capsules) ranging from a few to hundreds of nanometers. The chemical composition of the shell was tuned by varying the ratio of co-cross-linked shell-forming polymers (P4VP and PEI). In the second step, the hollow capsules were obtained by etching the silica core in HF solutions. In this step, the colloidal stability of the hollow capsules was provided by ionized P4VP and PEI cross-linked shells. The hollow capsules demonstrate that the pH- and ionic-strength-triggered swelling and shrinking result in size-selective uptake and release properties. Cross-linked via quaternized functional groups, P4VP capsules undergo swelling and shrinking transitions at a physiologically relevant pH of around 6. The 200-nm-diameter hollow capsule with 25-nm-thick walls demonstrated a factor of 2 greater capacity to accommodate cargo molecules than the core-shell particles of the same dimensions because of an internal compartment and a combination of radial and a circumferential swelling modes in the capsules. PMID:22053870
Motornov, Mikhail; Royter, Halyna; Lupitskyy, Robert; Roiter, Yuri; Minko, Sergiy
Efficient routes to carbon-silicon bond formation for the synthesis of silicon-containing peptides and azasilaheterocycles.
Silasubstitution, where silicon is substituted for carbon at specific sites of the substrate, has become a growing practice in medicinal chemistry. Introducing silicon into bioactive compounds provides slight physical and electronic alterations to the parent compound, which in certain instances could make the substrate a more viable candidate for a drug target. One application is in the field of protease inhibition. Various silane diol isosteres can act as potent inhibitors of aspartic and metalloproteases because of their ability to mimic the high-energy tetrahedral intermediate in peptide bond hydrolysis. In particular, since 1998, the Sieburth group has prepared a number of functionalized peptide silane diol isosteres. In a seminal study, they demonstrated that these molecules can bind to the active site of the enzymes. Inspired by these results, we initiated a study to develop a concise and straightforward route to access highly functionalized silicon diol based peptidomimetic analogs, which we describe in this Account. The synthesis of such analogs is challenging because the dipeptide mimics require the formation of two carbon-silicon bonds as well as two chiral carbon centers. Our first strategy was to assemble the two C-Si bonds from diphenylsilane through an initial regioselective hydrosilylation step of a terminal alkene, followed by lithiation of the formed alkyldiphenylsilane by a simple lithium metal reduction. Subsequent diastereoselective addition of this silyllithium species to a tert-butylsulfinimine provided a rapid method to assemble the dipeptide mimic with stereochemical control at the new chiral carbon center adjacent to the silicon. This strategy worked with a wide range of functional groups. However, there were some limitations with the more elaborate targets. In particular, we needed to exchange the phenyl groups of the diphenylsilane with aryl groups that were more labile under acidic conditions in order to introduce Si-O bonds in the end product. We demonstrated that a variety of Ar(2)SiH(2) compounds with methyl substituents on the aromatic core could effectively undergo hydrosilylation and reductive lithiation with a soluble reducing agent, lithium naphthalenide. The electron-rich aromatic groups were more acid labile and, depending on the conditions, could produce either the silane diol or the silanol. In an alternative strategy, we used a highly regioselective Rh-catalyzed sequential double hydrosilylation to form the two C-Si bonds with a single catalyst. This approach is a more efficient, atom economical way to synthesize a wider range of highly functionalized organosilanes with the added possibility of extending this method into an asymmetric protocol. By this method, various functional groups that were not previously tolerated in the lithiation protocol, including OBn, OAc, furyl, and thiophenes, could now be incorporated. Hydrosilylation of a terminal olefin and a peptide functionalized with an enamide at the C-terminus achieved the desired silane in high yields in a one pot reaction without compromising the stereochemical integrity of the peptide. As an extension of this work, we used these methods to efficiently generate a variety of chiral azasilaheterocycles, including silapiperidines and silaindolizidines. PMID:23214467
Min, Geanna K; Hern�ndez, D�cil; Skrydstrup, Troels
Sulfonic acid functionalized nano-?-Al2O3: a new, efficient, and reusable catalyst for synthesis of 3-substituted-2H-1,4-benzothiazines.
A simple and efficient synthetic protocol has been developed for the synthesis of 3-substituted-2H-1,4-benzothiazines by using a novel sulfonic acid functionalized nano-?-Al2O3 catalyst, devoid of corrosive acidic, and basic reagents. The developed method has the advantages of good to excellent yields, short reaction times, operational simplicity, and a recyclable catalyst. The catalyst can be prepared by a simple procedure from inexpensive and readily available nano-?-Al2O3 and has been shown to be recoverable and reusable up to six cycles without any loss of activity. PMID:23935435
Li, Wei Lin; Tian, Shuan Bao; Zhu, Feng
Efficient and large-scale synthesis of few-layered graphene using an arc-discharge method and conductivity studies of the resulting films
An arc-discharge method using a buffer gas containing carbon dioxide has been developed for the efficient and large-scale\\u000a synthesis of few-layered graphene. The resulting samples of few-layered graphene, well-dispersed in organic solvents such\\u000a as N,N-dimethylformamide (DMF) and 1,2-dichlorobenzene (o-DCB), were examined by transmission electron microscopy (TEM), X-ray diffraction (XRD), Raman spectroscopy, atomic force\\u000a microscopy (AFM), and thermal gravimetric analysis (TGA).
Yingpeng Wu; Bin Wang; Yanfeng Ma; Yi Huang; Na Li; Fan Zhang; Yongsheng Chen
An efficient procedure for traceless solid-phase synthesis of N,N'-substituted thioureas by thermolytic cleavage of resin-bound dithiocarbamates.
A novel and efficient procedure which is compatible with high-throughput process for the traceless solid-phase synthesis of thioureas is described. In the presence of carbon disulfide, Merrifield resin reacts with an amine to give a resin-bound dithiocarbamate moiety. Heating this supported dithiocarbamate in the presence of a second amine at 60 degrees C for 12 h led to the formation of the thiourea with the release of benzylthiol bound to the resin. This process allows the preparation of N,N'-di- and trisubstituted thioureas in good yields and with satisfactory purity. Furthermore, the mild reaction conditions involved are compatible with many functional groups. PMID:10750487
Gomez, L; Gellibert, F; Wagner, A; Mioskowski, C
Efficient synthesis of carbazoles via PtCl2-catalyzed RT cyclization of 1-(indol-2-yl)-2,3-allenols: scope and mechanism.
A detailed study on the scope of the efficient PtCl(2)-catalyzed synthesis of carbazoles from 1-(indol-2-yl)-2,3-allenols is described. Through isotopic labeling experiments, it is confirmed that the reaction proceeds through a unique metal carbene intermediate, which undergoes subsequent highly selective 1,2-hydrogen migration to afford carbazoles. The reaction shows wide scope and allows the introduction of a variety of different substituents at different positions on the carbazole due to the substituent-loading capability of both indole and the allene moiety. PMID:22299129
Kong, Wangqing; Fu, Chunling; Ma, Shengming
Copper ferrite nanoparticles: an efficient and reusable nanocatalyst for a green one-pot, three-component synthesis of spirooxindoles in water.
A green reaction of isatins, active cyanomethanes, and cyclic 1,3-dicarbonyl derivatives for the efficient and simple one-pot three-component synthesis of spirooxindole fused heterocycles in refluxing water by use of magnetically recoverable and reusable catalyst is reported. The features of this procedure are, the use of magnetically recoverable and reusable catalyst, mild reaction conditions, high to excellent product yields, operational simplicity, and easy workup procedures. Most importantly of all, easy magnetic separation of the catalyst eliminates the requirement of catalyst filtration after completion of the reaction. Furthermore, the catalyst remained highly active even after 5 repeated uses. PMID:24050156
Bazgir, Ayoob; Hosseini, Ghaffar; Ghahremanzadeh, Ramin
An efficient solvent-free synthesis of 2-hydroxy-2-(trifluoromethyl)-2H-chromenes using silica-immobilized L-proline.
An efficient synthesis of 2-hydroxy-2-(trifluoromethyl)-2H-chromene-3-carboxylates was carried out under solvent-free conditions in an oven or microwave oven via the Knoevenagel condensation of salicylaldehydes with ethyl trifluoroacetoacetate followed by intramolecular cyclization in the presence of silica-immobilized L-proline. The structures of the title compounds were characterized by IR, �H-NMR, ��C-NMR, HRMS and X-ray single crystal diffraction. The improved method described herein is economical, easily-operated and environmentally friendly. Furthermore, the catalyst can be recovered conveniently and reused without obvious loss of activity. PMID:24077175
Xu, Cuilian; Yang, Guoyu; Wang, Caixia; Fan, Sufang; Xie, Lixia; Gao, Ya
An efficient ruthenium-catalyzed dehydrogenative synthesis of 2,4,6-triaryl-1,3,5-triazines from aryl methanols and amidines.
By using [RuCl2(p-Cymene)]2/Cs2CO3 as an efficient catalyst system, the readily available, inexpensive aryl methanols were firstly employed for dehydrogenative synthesis of aryl substituted 1,3,5-triazine derivatives. Due to the inherent stability of alcohols in contrast with aldehydes, our synthetic protocol is adaptable to a broad substrate scope, there is no need for stringent protection during the whole operation process, and it has the potential to prepare valuable products that are currently inaccessible or challenging to prepare using conventional methods. It is a significantly important complement to the conventional synthetic methodologies. PMID:24668255
Xie, Feng; Chen, Mengmeng; Wang, Xiaoting; Jiang, Huanfeng; Zhang, Min
Key Building Blocks via Enzyme-Mediated Synthesis
Biocatalytic approaches to valuable building blocks in organic synthesis have emerged as an important tool in the last few years. While first applications were mainly based on hydrolases, other enzyme classes such as oxidoreductases or lyases moved into the focus of research. Nowadays, a vast number of biotransformations can be found in the chemical and pharmaceutical industries delivering fine chemicals or drugs. The mild reaction conditions, high stereo-, regio-, and chemoselectivities, and the often shortened reaction pathways lead to economical and ecological advantages of enzymatic conversions. Due to the enormous number of enzyme-mediated syntheses, the present chapter is not meant to be a complete review, but to deliver comprehensive insights into well established enzymatic systems and recent advances in the application of enzymes in natural product synthesis. Furthermore, it is focused on the most frequently used enzymes or enzyme classes not covered elsewhere in the present volume.
Fischer, Thomas; Pietruszka, J�rg
A strategy utilizing a recyclable macrocycle transporter for the efficient synthesis of a triazolium-based [2]rotaxane.
A general synthesis of triazolium-containing [2]rotaxanes, which could not be accessed by other methods, is reported. It is based on a sequential strategy starting from a well-designed macrocycle transporter which contains a template for dibenzo-24-crown-8 and a N-hydroxysuccinimide (NHS) moiety. The sequence is: 1)?synthesis by slippage of a [2]rotaxane building-block; 2)?its elongation at its NHS end; 3)?the delivery of the macrocycle to the elongated part of the axle by an induced translational motion; 4)?the contraction process to yield the targeted [2]rotaxane and recycle the initial transporter. PMID:24910397
Chao, Sovy; Romuald, Camille; Fournel-Marotte, Karine; Clavel, Caroline; Coutrot, Fr�d�ric
Limited Domain Synthesis.
National Technical Information Service (NTIS)
This work presents a reliable and efficient method for building limited domain speech synthesis voices. By constructing databases close to the targeted domain of the speech application, unit selection synthesis techniques can be used to reliably give very...
A. W. Black K. A. Lenzo
An efficient and versatile synthesis of GlcNAcstatins--potent and selective O-GlcNAcase inhibitors built on the tetrahydroimidazo[1,2-a]pyridine scaffold
We report a novel approach to the synthesis of GlcNAcstatins�members of an emerging family of potent and selective inhibitors of peptidyl O-GlcNAc hydrolase build upon tetrahydroimidazo[1,2-a]pyridine scaffold. Making use of a streamlined synthetic sequence featuring de novo synthesis of imidazoles from glyoxal, ammonia and aldehydes, a properly functionalised linear GlcNAcstatin precursor has been efficiently prepared starting from methyl 3,4-O-(2?,3?-dimethoxybutane-2?,3?-diyl)-?-d-mannopyranoside. Subsequent ring closure of the linear precursor in an intramolecular SN2 process furnished the key fused d-mannose-imidazole GlcNAcstatin precursor in excellent yield. Finally, a sequence of transformations of this key intermediate granted expeditious access to a variety of the target compounds bearing a C(2)-phenethyl group and a range of N(8) acyl substituents. The versatility of the new approach stems from an appropriate choice of a set of acid labile permanent protecting groups on the monosaccharide starting material. Application was demonstrated by the synthesis of GlcNAcstatins containing polyunsaturated and thiol-containing amido substituents.
Borodkin, Vladimir S.; van Aalten, Daan M.F.
Functionalization of hyaluronic acid with chemoselective groups via a disulfide-based protection strategy for in situ formation of mechanically stable hydrogels.
Functionalization of hyaluronic acid (HA) with chemoselective groups enables in situ (in vivo) formation of HA-based materials in minimally invasive injectable manner. Current methods of HA modification with such groups primarily rely on the use of a large excess of a reagent to introduce a unique reactive handle into HA and, therefore, are difficult to control. We have developed the new protective group strategy based on initial mild cleavage of a disulfide bond followed by elimination of the generated 2-thioethoxycarbonyl moiety ultimately affording free amine-type functionality, such as hydrazide, aminooxy, and carbazate. Specifically, new modifying homobifunctional reagents have been synthesized that contain a new divalent disulfide-based protecting group. Amidation of HA with these reagents gives rise to either one-end coupling product or to intra/intermolecular cross-linking of the HA chains. However, after subsequent treatment of the amidation reaction mixture with dithiothreitol (DTT), these cross-linkages are cleaved, ultimately exposing free amine-type groups. The same methodology was applied to graft serine residues to the HA backbone, which were subsequently oxidized into aldehyde groups. The strategy therefore encompasses a new approach for mild and highly controlled functionalization of HA with both nucleophilic and electrophilic chemoselective functionalities with the emphasis for the subsequent conjugation and in situ cross-linking. A series of new hydrogel materials were prepared by mixing the new HA-aldehyde derivative with different HA-nucleophile counterparts. Rheological properties of the formed hydrogels were determined and related to the structural characteristics of the gel networks. Human dermal fibroblasts remained viable while cultured with the hydrogels for 3 days, with no sign of cytotoxicity, suggesting that the gels described in this study are candidates for use as growth factors delivery vehicles for tissue engineering applications. PMID:20704177
Ossipov, Dmitri A; Piskounova, Sonya; Varghese, Oommen P; Hilborn, J�ns
Mixed lipases for efficient enzymatic synthesis of biodiesel from used palm oil and ethanol in a solvent-free system
The enzymatic synthesis of biodiesel from used palm oil and ethanol using immobilized lipases in a solvent-free system was attempted. Five immobilized lipases, Lipase AK from Pseudomonas fluorescens, Lipase PS from Pseudomonas cepacia, Lipase AY from Candida rugosa, Lipozyme TL IM from Thermomyces lanuginosa and Novozym 435 from Candida antarctica, were screened based on their catalytic activities on reactions involved
Ketsara Tongboriboon; Benjamas Cheirsilp; Aran H-Kittikun
Highly efficient and economic synthesis of new substituted amino-bispyridyl derivatives via copper and palladium catalysis
A convenient route for the synthesis of a variety of amino-bispyridyl compounds is introduced. Bispyridylamines were prepared in three steps from commercially available 2,6-dibromopyridine, via a copper mediated alkylation followed by two consecutive N-arylation reactions catalyzed by copper and palladium, respectively.
Sylvain Gaillard; Mohammed Kamal Elmkaddem; C�dric Fischmeister; Christophe M. Thomas; Jean-Luc Renaud
Efficient biocatalyst for large-scale synthesis of cephalosporins, obtained by combining immobilization and site-directed mutagenesis of penicillin acylase.
We describe the rational design of a new efficient biocatalyst and the development of a sustainable green process for the synthesis of cephalosporins bearing a NH? group on the acyl side chain. The new biocatalyst was developed starting from the WT penicillin acylase (PA) from Escherichia coli by combining enzyme mutagenesis, in position ?146 and ?24 (?F24A/?F146Y), and immobilization on an appropriate modified industrial support, glyoxyl Eupergit C250L. The obtained derivative was used in the kinetically controlled synthesis of cephalexin, cefprozil and cefaclor and compared to the WT-PA and an already described mutant, PA-?F24A, with improved properties. The new biocatalyst posses a very high ratio between the rates of the synthesis and two undesired hydrolyses (acylating ester and the amidic product). In particular, a very low amidase activity was observed with PA-?F24A/?F146Y and, consequently, the hydrolysis of the produced antibiotic was avoided during the process. Taking advantage of this property, higher conversions in the synthesis of cephalexin (99% versus 76%), cefaclor (99% versus 65%) and cefprozil (99% versus 60%) were obtained compared to the WT enzyme. Furthermore, the new mutant also show a higher synthetic activity compared to PA-?F24A immobilized on the same support, allowing the maximum yields to be achieved in very short reaction times. The production of cephalexin with the immobilized ?F24A/?F146Y acylase has been developed on a pre-industrial scale (30 l). After 20 cycles, the average yield was 93%. The biocatalyst showed good stability properties and no significant decrease in performance. PMID:22228258
Cecchini, Davide A; Pavesi, Roberto; Sanna, Sara; Daly, Simona; Xaiz, Roberto; Pregnolato, Massimo; Terreni, Marco
Novel one-pot, four-component condensation reaction: an efficient approach for the synthesis of 2,5-disubstituted 1,3,4-oxadiazole derivatives by a Ugi-4CR/aza-Wittig sequence.
A novel and efficient method has been developed for the synthesis of 2,5-disubstituted 1,3,4-oxadiazole derivatives using (N-isocyanimino)triphenylphosphorane, a secondary amine, a carboxylic acid, and an aromatic aldehyde in CH(2)Cl(2) at ambient temperature in high yields without using any catalyst or activation. The procedure provides an alternative method to the synthesis of fully substituted 1,3,4-oxadiazole derivatives. PMID:20481612
Ramazani, Ali; Rezaei, Aram
One-pot synthesis and cytotoxicity studies of new Mannich base derivatives of polyether antibiotic--lasalocid acid.
Seven Mannich base derivatives of polyether antibiotic Lasalocid acid (2a-2g) were synthesized and screened for their antiproliferative activity against various human cancer cell lines. A novel chemoselective one-pot synthesis of these Mannich bases was developed. Compounds 2a-2c and 2g with sterically smaller dialkylamine substituent, displayed potent antiproliferative activity (IC50: 3.2-7.3 ?M), and demonstrated higher than twofold selectivity for specific type of cancer. The nature of Mannich base substituent on C-2 atom at the aromatic ring may be critical in the search for selectivity towards a particular cancer cell. PMID:23932361
Huczy?ski, Adam; Rutkowski, Jacek; Borowicz, Izabela; Wietrzyk, Joanna; Maj, Ewa; Brzezinski, Bogumil
CTAB-assisted synthesis of monoclinic BiVO4 photocatalyst and its highly efficient degradation of organic dye under visible-light irradiation.
A highly efficient monoclinic BiVO(4) photocatalyst (C-BVO) was synthesized by an aqueous method with the assistance of cetyltrimethylammonium bromide (CTAB). The structure, morphology and photophysical properties of the C-BVO were characterized by XRD, FE-SEM and diffuse reflectance spectroscopy, respectively. The photocatalytic efficiencies were evaluated by the degradation of rhodamine B (RhB) under visible-light irradiation, revealing that the degradation rate over the C-BVO was much higher than that over the reference BiVO(4) prepared by aqueous method and over the one prepared by solid-state reaction. The efficiency of de-ethylation and that of the cleavage of conjugated chromophore structure were investigated, respectively. The chemical oxygen demand (COD) values of the RhB were measured after the photocatalytic degradation over the C-BVO and demonstrated a 53% decrease in COD. The effects of CTAB on the synthesis of C-BVO were investigated, which revealed that CTAB not only changed the reaction process via the formation of BiOBr as an intermediate, but also facilitated the transition from BiOBr to BiVO(4). Comparison experiments were carried out and showed that the existence of impurity level makes significant contribution to the high photocatalytic efficiency of the C-BVO. PMID:19733435
Yin, Wenzong; Wang, Wenzhong; Zhou, Lin; Sun, Songmei; Zhang, Ling
Novel Protocol for the Chemical Synthesis of Crustacean Hyperglycemic Hormone Analogues -- An Efficient Experimental Tool for Studying Their Functions
The crustacean Hyperglycemic Hormone (cHH) is present in many decapods in different isoforms, whose specific biological functions are still poorly understood. Here we report on the first chemical synthesis of three distinct isoforms of the cHH of Astacus leptodactylus carried out by solid phase peptide synthesis coupled to native chemical ligation. The synthetic 72 amino acid long peptide amides, containing L- or D-Phe3 and (Glp1, D-Phe3) were tested for their biological activity by means of homologous in vivo bioassays. The hyperglycemic activity of the D-isoforms was significantly higher than that of the L-isoform, while the presence of the N-terminal Glp residue had no influence on the peptide activity. The results show that the presence of D-Phe3 modifies the cHH functionality, contributing to the diversification of the hormone pool.
Mosco, Alessandro; Zlatev, Vientsislav; Guarnaccia, Corrado; Pongor, Sandor; Campanella, Antonella; Zahariev, Sotir; Giulianini, Piero G.
Lewis base mediated efficient synthesis and solvation-like host-guest chemistry of covalent organic framework-1.
N-Lewis base mediated room temperature synthesis of covalent organic frameworks (COFs) starting from a solution of building blocks instead of partially soluble building blocks was developed. This protocol shifts COF synthetic chemistry from sealed tubes to open beakers. Non-conventional inclusion compounds of COF-1 were obtained by vapor phase infiltration of ferrocene and azobenzene, and solvation like effects were established. PMID:23208512
Kalidindi, Suresh Babu; Wiktor, Christian; Ramakrishnan, Ayyappan; We�ing, Jana; Schneemann, Andreas; Van Tendeloo, Gustaaf; Fischer, Roland A
Efficient synthesis of dimethyl carbonate via transesterification of ethylene carbonate with methanol over binary zinc-yttrium oxides
The binary zinc�yttrium oxides were prepared by co-precipitation method, characterized and tested in the synthesis of DMC via transesterification of ethylene carbonate with methanol. The catalytic results showed that the catalyst with Zn\\/Y molar ratio of 3 and calcined at 400�C exhibited superior catalytic activity, corresponding to TOF of 236mmol\\/gcath. Appropriate content of yttrium in the catalyst enhanced the catalytic
Liguo Wang; Ying Wang; Shimin Liu; Liujin Lu; Xiangyuan Ma; Youquan Deng
Efficient Synthesis of 1,5-Disubstituted Carbohydrazones Using K2CO3 As a Carbonyl Donor.
A novel reaction that generates 1,5-disubstituted carbohydrazones via the carbonylation of tosylhydrazones has been developed. For the first time, the inexpensive, readily available, environmentally friendly, and nongaseous potassium carbonate is used as the carbonyl donor for the transformation. The reaction system exhibited tolerance with various functional groups and affords the desired products in good to excellent yields. This reaction is expected to be a powerful tool for the synthesis of carbohydrazone compounds. PMID:24738977
Wen, Jun; Yang, Chu-Ting; Jiang, Tao; Hu, Sheng; Yang, Tong-Zai; Wang, Xiao-Lin
Variants of mouse DNA polymerase ? reveal a mechanism of efficient and accurate translesion synthesis past a benzo[a]pyrene dG adduct.
DNA polymerase ? (Pol?) is the only known Y-family DNA polymerase that bypasses the 10S (+)-trans-anti-benzo[a]pyrene diol epoxide (BPDE)-N(2)-deoxyguanine adducts efficiently and accurately. The unique features of Pol?, a large structure gap between the catalytic core and little finger domain and a 90-residue addition at the N terminus known as the N-clasp, may give rise to its special translesion capability. We designed and constructed two mouse Pol? variants, which have reduced gap size on both sides [Pol? Gap Mutant (PGM) 1] or one side flanking the template base (PGM2). These Pol? variants are nearly as efficient as WT in normal DNA synthesis, albeit with reduced accuracy. However, PGM1 is strongly blocked by the 10S (+)-trans-anti-BPDE-N(2)-dG lesion. Steady-state kinetic measurements reveal a significant reduction in efficiency of dCTP incorporation opposite the lesion by PGM1 and a moderate reduction by PGM2. Consistently, Pol?-deficient cells stably complemented with PGM1 GFP-Pol? remained hypersensitive to BPDE treatment, and complementation with WT or PGM2 GFP-Pol? restored BPDE resistance. Furthermore, deletion of the first 51 residues of the N-clasp in mouse Pol? (mPol?(52-516)) leads to reduced polymerization activity, and the mutant PGM2(52-516) but not PGM1(52-516) can partially compensate the N-terminal deletion and restore the catalytic activity on normal DNA. However, neither WT nor PGM2 mPol?(52-516) retains BPDE bypass activity. We conclude that the structural gap physically accommodates the bulky aromatic adduct and the N-clasp is essential for the structural integrity and flexibility of Pol? during translesion synthesis. PMID:24449898
Liu, Yang; Yang, Yeran; Tang, Tie-Shan; Zhang, Hui; Wang, Zhifeng; Friedberg, Errol; Yang, Wei; Guo, Caixia
Phosphatidylethanolamine synthesis in the parasite mitochondrion is required for efficient growth but dispensable for survival of Toxoplasma gondii.
Toxoplasma gondii is a highly prevalent obligate intracellular parasite of the phylum Apicomplexa, which also includes other parasites of clinical and/or veterinary importance, such as Plasmodium, Cryptosporidium, and Eimeria. Acute infection by Toxoplasma is hallmarked by rapid proliferation in its host cells and requires a significant synthesis of parasite membranes. Phosphatidylethanolamine (PtdEtn) is the second major phospholipid class in T. gondii. Here, we reveal that PtdEtn is produced in the parasite mitochondrion and parasitophorous vacuole by decarboxylation of phosphatidylserine (PtdSer) and in the endoplasmic reticulum by fusion of CDP-ethanolamine and diacylglycerol. PtdEtn in the mitochondrion is synthesized by a phosphatidylserine decarboxylase (TgPSD1mt) of the type I class. TgPSD1mt harbors a targeting peptide at its N terminus that is required for the mitochondrial localization but not for the catalytic activity. Ablation of TgPSD1mt expression caused up to 45% growth impairment in the parasite mutant. The PtdEtn content of the mutant was unaffected, however, suggesting the presence of compensatory mechanisms. Indeed, metabolic labeling revealed an increased usage of ethanolamine for PtdEtn synthesis by the mutant. Likewise, depletion of nutrients exacerbated the growth defect (?56%), which was partially restored by ethanolamine. Besides, the survival and residual growth of the TgPSD1mt mutant in the nutrient-depleted medium also indicated additional routes of PtdEtn biogenesis, such as acquisition of host-derived lipid. Collectively, the work demonstrates a metabolic cooperativity between the parasite organelles, which ensures a sustained lipid synthesis, survival and growth of T. gondii in varying nutritional milieus. PMID:24429285
Hartmann, Anne; Hellmund, Maria; Lucius, Richard; Voelker, Dennis R; Gupta, Nishith
The role of ?6-desaturase acyl-carrier specificity in the efficient synthesis of long-chain polyunsaturated fatty acids in transgenic plants.
The role of acyl-CoA-dependent ?6-desaturation in the heterologous synthesis of omega-3 long-chain polyunsaturated fatty acids was systematically evaluated in transgenic yeast and Arabidopsis thaliana. The acyl-CoA ?6-desaturase from the picoalga Ostreococcus tauri and orthologous activities from mouse (Mus musculus) and salmon (Salmo salar) were shown to generate substantial levels of ?6-desaturated acyl-CoAs, in contrast to the phospholipid-dependent ?6-desaturases from higher plants that failed to modify this metabolic pool. Transgenic plants expressing the acyl-CoA ?6-desaturases from either O.�tauri or salmon, in conjunction with the two additional activities required for the synthesis of C20 polyunsaturated fatty acids, contained higher levels of eicosapentaenoic acid compared with plants expressing the borage phospholipid-dependent ?6-desaturase. The use of acyl-CoA-dependent ?6-desaturases almost completely abolished the accumulation of unwanted biosynthetic intermediates such as ?-linolenic acid in total seed lipids. Expression of acyl-CoA ?6-desaturases resulted in increased distribution of long-chain polyunsaturated fatty acids in the polar lipids of transgenic plants, reflecting the larger substrate pool available for acylation by enzymes of the Kennedy pathway. Expression of the O.�tauri?6-desaturase in transgenic Camelina sativa plants also resulted in the accumulation of high levels of ?6-desaturated fatty acids. This study provides evidence for the efficacy of using acyl-CoA-dependent ?6-desaturases in the efficient metabolic engineering of transgenic plants with high value traits such as the synthesis of omega-3 LC-PUFAs. PMID:21902798
Sayanova, Olga; Ruiz-Lopez, Noemi; Haslam, Richard P; Napier, Johnathan A
Efficient synthesis of novel glutamate homologues and investigation of their affinity and selectivity profile at ionotropic glutamate receptors.
A convenient synthesis of four new enantiomerically pure acidic amino acids is reported and their affinity at ionotropic glutamate receptors was determined. The new compounds are higher homologues of glutamic acid in which the molecular complexity has been increased by introducing an aromatic/heteroaromatic ring, that is a phenyl or a thiophene ring, that could give additional electronic interactions with the receptors. The results of the present investigation indicate that the insertion of an aromatic/heteroaromatic ring into the amino acid skeleton of glutamate higher homologues is well tolerated and this modification could be exploited to generate a new class of NMDA antagonists. PMID:24630559
Pinto, Andrea; Tamborini, Lucia; Mastronardi, Federica; Ettari, Roberta; Romano, Diego; Nielsen, Birgitte; De Micheli, Carlo; Conti, Paola
The versatile enzyme Araf51 allowed efficient synthesis of rare pathogen-related ?-D-galactofuranosyl-pyranoside disaccharides.
The preparation of galactofuranosyl-containing disaccharidic parts of natural glycoconjugates was performed according to a chemo-enzymatic synthesis. Our goals were firstly to develop an alternative approach to standard chemical strategies by limiting the number of reaction and purification steps, and secondly to evaluate the scope of the Araf51 biocatalyst to transfer a galactofuranosyl moiety to a set of pyranosidic acceptors differing from each other by the series, the anomeric configuration as well as the conformation. The study of binding mode of the resulting disaccharides was also performed by molecular modeling and showed significant differences between (1?2)- and (1?6)-linked disaccharides. PMID:24700171
Chlubnov�, Ilona; Kr�lov�, Blanka; Dvo?�kov�, Hana; Ho�ek, Petr; Spiwok, Vojt?ch; Filipp, Dominik; Nugier-Chauvin, Caroline; Daniellou, Richard; Ferri�res, Vincent
Microwave-assisted four-component, one-pot condensation reaction: an efficient synthesis of annulated pyridines.
A one-pot, effective synthesis of pyridines by a modified Kr�hnke procedure is described. Polysubstituted annulated pyridines were synthesized in high yields by four-component, one-pot cyclocondensation reactions of N-phenacylpyridinium bromide, aromatic aldehydes, acetophenones or cyclic ketones in the presence of ammonium acetate and acetic acid, assisted by microwave irradiation. In this procedure, cyclic ketones with two alpha-CH(2) groups yield annulated pyridines with additional alpha-benzylidene groups, which are derived in situ from double aldol condensation of cyclic ketones with two moles of aromatic aldehydes. PMID:17340010
Yan, Chao-Guo; Cai, Xi-Mei; Wang, Qi-Fang; Wang, Ting-Yu; Zheng, Ming
An efficient protocol for the synthesis of quinoxaline derivatives at room temperature using recyclable alumina-supported heteropolyoxometalates.
We report a suitable quinoxaline synthesis using molybdophosphovanadates supported on commercial alumina cylinders as catalysts. These catalysts were prepared by incipient wetness impregnation. The catalytic test was performed under different reaction conditions in order to know the performance of the synthesized catalysts. The method shows high yields of quinoxaline derivatives under heterogeneous conditions. Quinoxaline formation was obtained using benzyl, o-phenylenediamine, and toluene as reaction solvent at room temperature. The CuH(2)PMo(11)VO(40) supported on alumina showed higher activity in the tested reaction. Finally, various quinoxalines were prepared under mild conditions and with excellent yields. PMID:22536123
Ruiz, Diego M; Autino, Juan C; Quaranta, Nancy; V�zquez, Patricia G; Romanelli, Gustavo P
An Efficient Protocol for the Synthesis of Quinoxaline Derivatives at Room Temperature Using Recyclable Alumina-Supported Heteropolyoxometalates
We report a suitable quinoxaline synthesis using molybdophosphovanadates supported on commercial alumina cylinders as catalysts. These catalysts were prepared by incipient wetness impregnation. The catalytic test was performed under different reaction conditions in order to know the performance of the synthesized catalysts. The method shows high yields of quinoxaline derivatives under heterogeneous conditions. Quinoxaline formation was obtained using benzyl, o-phenylenediamine, and toluene as reaction solvent at room temperature. The CuH2PMo11VO40 supported on alumina showed higher activity in the tested reaction. Finally, various quinoxalines were prepared under mild conditions and with excellent yields.
Ruiz, Diego M.; Autino, Juan C.; Quaranta, Nancy; Vazquez, Patricia G.; Romanelli, Gustavo P.
High-Efficiency Synthesis of Human ?-Endorphin and Magainin in the Erythrocytes of Transgenic Mice: A Production System for Therapeutic Peptides
Chemical synthesis of peptides, though feasible, is hindered by considerations of cost, purity, and efficiency of synthesizing longer chains. Here we describe a transgenic system for producing peptides of therapeutic interest as fusion proteins at low cost and high purity. Transgenic hemoglobin expression technology using the locus control region was employed to produce fusion hemoglobins in the erythrocytes of mice. The fusion hemoglobin contains the desired peptide as an extension at the C end of human ?-globin. A protein cleavage site is inserted between the C end of the ?-globin chain and the N-terminal residue of the desired peptide. The peptide is recovered after cleavage of the fusion protein with enzymes that recognize this cleavage signal as their substrate. Due to the selective compartmentalization of hemoglobin in the erythrocytes, purification of the fusion hemoglobin is easy and efficient. Because of its compact and highly ordered structure, the internal sites of hemoglobin are resistant to protease digestion and the desired peptide is efficiently released and recovered. The applicability of this approach was established by producing a 16-mer ?-endorphin peptide and a 26-mer magainin peptide in transgenic mice. Transgenic animals and their progeny expressing these fusion proteins remain healthy, even when the fusion protein is expressed at >25% of the total hemoglobin in the erythrocytes. Additional applications and potential improvements of this methodology are discussed.
Sharma, Ajay; Khoury-Christianson, Anastasia M.; White, Steven P.; Dhanjal, Nirpal K.; Huang, Wen; Paulhiac, Clara; Friedman, Eric J.; Manjula, Belur N.; Kumar, Ramesh
Carbohydrate-Binding Module-Cyclodextrin Glycosyltransferase Fusion Enables Efficient Synthesis of 2-O-d-Glucopyranosyl-l-Ascorbic Acid with Soluble Starch as the Glycosyl Donor
In this study, we achieved the efficient synthesis of 2-O-d-glucopyranosyl-l-ascorbic acid (AA-2G) from soluble starch by fusing a carbohydrate-binding module (CBM) from Alkalimonas amylolytica ?-amylase (CBMAmy) to cyclodextrin glycosyltransferase (CGTase) from Paenibacillus macerans. One fusion enzyme, CGT-CBMAmy, was constructed by fusing the CBMAmy to the C-terminal region of CGTase, and the other fusion enzyme, CGT?E-CBMAmy, was obtained by replacing the E domain of CGTase with CBMAmy. The two fusion enzymes were then used to synthesize AA-2G from soluble starch as a cheap and easily soluble glycosyl donor. Under the optimal conditions, the AA-2G yields produced using CGT?E-CBMAmy and CGT-CBMAmy were 2.01 g/liter and 3.03 g/liter, respectively, which were 3.94- and 5.94-fold of the yield from the wild-type CGTase (0.51 g/liter). The reaction kinetics of the two fusion enzymes were analyzed and modeled to confirm the enhanced specificity toward soluble starch. It was also found that, compared to the wild-type CGTase, the two fusion enzymes had relatively high hydrolysis and disproportionation activities, factors that favor AA-2G synthesis. Finally, it was speculated that the enhancement of soluble starch specificity may be related to the changes of substrate binding ability and the substrate binding sites between the CBM and the starch granule.
Han, Ruizhi; Li, Jianghua; Shin, Hyun-Dong; Chen, Rachel R.; Du, Guocheng
Carbohydrate-binding module-cyclodextrin glycosyltransferase fusion enables efficient synthesis of 2-O-d-glucopyranosyl-l-ascorbic acid with soluble starch as the glycosyl donor.
In this study, we achieved the efficient synthesis of 2-O-d-glucopyranosyl-l-ascorbic acid (AA-2G) from soluble starch by fusing a carbohydrate-binding module (CBM) from Alkalimonas amylolytica ?-amylase (CBMAmy) to cyclodextrin glycosyltransferase (CGTase) from Paenibacillus macerans. One fusion enzyme, CGT-CBMAmy, was constructed by fusing the CBMAmy to the C-terminal region of CGTase, and the other fusion enzyme, CGT?E-CBMAmy, was obtained by replacing the E domain of CGTase with CBMAmy. The two fusion enzymes were then used to synthesize AA-2G from soluble starch as a cheap and easily soluble glycosyl donor. Under the optimal conditions, the AA-2G yields produced using CGT?E-CBMAmy and CGT-CBMAmy were 2.01 g/liter and 3.03 g/liter, respectively, which were 3.94- and 5.94-fold of the yield from the wild-type CGTase (0.51 g/liter). The reaction kinetics of the two fusion enzymes were analyzed and modeled to confirm the enhanced specificity toward soluble starch. It was also found that, compared to the wild-type CGTase, the two fusion enzymes had relatively high hydrolysis and disproportionation activities, factors that favor AA-2G synthesis. Finally, it was speculated that the enhancement of soluble starch specificity may be related to the changes of substrate binding ability and the substrate binding sites between the CBM and the starch granule. PMID:23503312
Han, Ruizhi; Li, Jianghua; Shin, Hyun-Dong; Chen, Rachel R; Du, Guocheng; Liu, Long; Chen, Jian
An innovative approach for efficient and reusable catalization for synthesis of α, β-unsaturated compounds using polymer - NPs composites as catalyst
Catalyst plays an important role in many of synthesis and chemical reactions, like ?,?-unsaturated products cannot be synthesized without presence of suitable catalyst, but for efficient catalization of reactions catalyst must have high surface area as well as they must be easily removed after termination of reaction without leaving an impurity in final product. To achieve both of these conditions an innovative approach is used. Here Polycarbonate (PC)-ZnO NPs composites membranes have been successfully fabricated by solution casting technique in where ZnO NPs (45nm) acts as a catalyst with increased surface area, while as these catalyst are embedded in PC matrix that can be easily removed after termination of reaction. Membranes were characterized via different techniques like SEM, FTIR etc. Activity of this nanocomposite based catalytic system for the stereoselective synthesis of ?, ?-unsaturated compounds is tested and found increased in yield of compounds with increase in concentration of ZnO nanoparticle content upto 5%. Above this at high ZnO loadings (9%) slight agglomeration of NPs occurred which hindered the catalytic effect of Nano composite.
Pimpliskar, Prashant; Bagra, Bhawna; Kumar, Gautam Aashish; Khandelwal, Saurabh; Agrawal, Narendra Kumar
Efficient Synthesis of Primary Amides from Carboxylic Acids using N,N?-Carbonyldiimidazole and Ammonium Acetate in Ionic Liquid
A novel and efficient method for the conversion of carboxylic acids to primary amides using N,N?-carbonyldiimidazole in combination with ammonium acetate\\/triethyl amine system in [BMIM]BF4 is developed.
Kwan Soo Lee; Kee D. Kim
Oxyma: an efficient additive for peptide synthesis to replace the benzotriazole-based HOBt and HOAt with a lower risk of explosion.
Oxyma [ethyl 2-cyano-2-(hydroxyimino)acetate] has been tested as an additive for use in the carbodiimide approach for formation of peptide bonds. Its performance in relation to those of HOBt and HOAt, which have recently been reported to exhibit explosive properties, is reported. Oxyma displayed a remarkable capacity to inhibit racemization, together with impressive coupling efficiency in both automated and manual synthesis, superior to those of HOBt and at least comparable to those of HOAt, and surpassing the latter coupling agent in the more demanding peptide models. Stability assays showed that there was no risk of capping the resin under standard coupling conditions. Finally, calorimetry assays (DSC and ARC) showed decomposition profiles for benzotriazole-based additives that were consistent with their reported explosivities and suggested a lower risk of explosion in the case of Oxyma. PMID:19575348
Subir�s-Funosas, Ramon; Prohens, Rafel; Barbas, Rafael; El-Faham, Ayman; Albericio, Fernando
Aqueous SDS micelle-promoted acid-catalyzed domino ABB' imino Diels-Alder reaction: a mild and efficient synthesis of privileged 2-methyl-tetrahydroquinoline scaffolds.
A new green protocol for the efficient synthesis of pharmacologically relevant 4-amidyl-2-methyl-1,2,3,4-tetrahydroquinolines (THQs) through the domino type ABB' imino Diels-Alder reaction in acidified water in the presence of sodium dodecyl sulphate (SDS) surfactant was developed for the first time. The influence of the SDS micelles and their different concentrations (5.0, 8.2 and 12.0 mM) on reactivity of the imino Diels-Alder reaction was studied. It was found that the best THQ yields (70-99%) are achieved above the critical micellar concentration (12 mM) using pH 1.0-2.5. This procedure resulted in a general and clean environmentally benign protocol to obtain the privileged diastereospecific cis 2,4-disubstituted THQ molecules of highest biological interest. PMID:23615634
Merch�n Arenas, Diego R; Mart�nez Bonilla, Carlos A; Kouznetsov, Vladimir V
Phosphomolybdic and phosphotungstic acids as efficient catalysts for the synthesis of bridged 1,2,4,5-tetraoxanes from ?-diketones and hydrogen peroxide.
Phosphomolybdic acid (PMA) and phosphotungstic acid (PTA) efficiently catalyze the addition of H2O2 to ?-diketones to form bridged 1,2,4,5-tetraoxanes. These reactions are not accompanied by the formation of monocyclic peroxides containing hydroxy and hydroperoxide groups or polymeric peroxides. The use of these catalysts made it possible to obtain bridged tetraoxanes from easily oxidizable benzoylacetone derivatives and ?-unsubstituted ?-diketones. The syntheses are scaled up to ten grams. The resulting peroxides can be easily isolated from the reaction mixture by column chromatography. The yield of tetraoxanes depends on the structure of ?-diketone and varies from 12 to 83%. NMR monitoring of two bridged 1,2,4,5-tetraoxanes synthesis was carried out. PMID:23446630
Terent'ev, Alexander O; Yaremenko, Ivan A; Vil', Vera A; Moiseev, Igor K; Kon'kov, Sergey A; Dembitsky, Valery M; Levitsky, Dmitri O; Nikishin, Gennady I
Simple Synthesis and Biological Evaluation of Some Benzimidazoles Using Sodium Hexafluroaluminate, Na 3 AlF 6 , as an Efficient Catalyst
Considerable attention has been focused on the synthesis of benzimidazoles due to having a broad spectrum of biological activities such as anti-parasitic, fungicidal, anti-thelemintic and anti-inflammatory activities. As a part of our research work in this area, a series of benzimidasole derivatives (3a-n) were synthesized in good to high yields by reaction of o-phenylenediamine and different aromatic aldehydes in the presence of sodium hexafluroaluminate, Na3AlF6, as an efficient catalyst at 50 ?C. This environmentally benign and practical method offers several advantages, such as high yields, use of available catalyst, mild reaction conditions and easy workup. The antibacterial activity of these benzimidasoles was also evaluated using Staphylococcus aureus (mm) and Escherichia coli (mm) bacterial strain. All synthesized materials were characterized using IR and NMR spectroscopy as well as microanalyses data.
Mobinikhaledi, Akbar; Hamta, Ahmad; Kalhor, Mehdi; Shariatzadeh, Mehdi
[11C]PR04.MZ, a promising DAT ligand for low concentration imaging: synthesis, efficient 11C-0-methylation and initial small animal PET studies
PR04.MZ was designed as a highly selective dopamine transporter inhibitor, derived from natural cocaine. Its binding profile indicates that [{sup 11}C]PR04.MZ may be suited as a PET radioligand for the non-invasive exploration of striatal and extrastriatal DAT populations. As a key feature, its structural design facilitates both, labelling with fluorine-18 at its terminally fluorinated butynyl moiety and carbon-11 at its methyl ester function. The present report concerns the efficient [{sup 11}C]MeI mediated synthesis of [{sup 11}C]PR04.MZ from an O-desmethyl precursor trifluoroacetic acid salt with Rb{sub 2}CO{sub 3} in DMF in up to 95 {+-} 5% labelling yield. A preliminary {mu}PET-experiment demonstrates the reversible, highly specific binding of [{sup 11}C]PR04.MZ in the brain of a male Sprague-Dawley rat.
Riss, P.J.; Hooker, J.; Alexoff, D.; Kim, Sung-Won; Fowler, J.S.; Roesch, F.
Biomolecule-assisted synthesis of carbon nitride and sulfur-doped carbon nitride heterojunction nanosheets: An efficient heterojunction photocatalyst for photoelectrochemical applications
Summary A biomolecule-assisted pyrolysis method has been developed to synthesize sulfur-doped graphitic carbon nitride (CNS) nanosheets. During the synthesis, sulfur could be introduced as a dopant into the lattice of carbon nitride (CN). Sulfur doping changed the texture as well as relative band positions of CN. By growing CN on preformed sulfur-doped CN nanosheets, composite CN/CNS heterojunction nanosheets were constructed, which significantly enhanced the photoelectrochemical performance as compared with various control counterparts including CN, CNS and physically mixed CN and CNS (CN+CNS). The enhanced photoelectrochemical performance of CN/CNS heterojunction nanosheets could be ascribed to the efficient separation of photoexcited charge carriers across the heterojunction interface. The strategy of designing and preparing CN/CNS heterojunction photocatalysts in this work can open up new directions for the construction of all CN-based heterojunction photocatalysts.
Tao, Hua Bing; Chen, Jiazang; Miao, Jianwei
Translation of microwave methodology to continuous flow for the efficient synthesis of diaryl ethers via a base-mediated SNAr reaction
Summary Whilst microwave heating has been widely demonstrated as a synthetically useful tool for rapid reaction screening, a microwave-absorbing solvent is often required in order to achieve efficient reactant heating. In comparison, microreactors can be readily heated and pressurised in order to �super-heat� the reaction mixture, meaning that microwave-transparent solvents can also be employed. To demonstrate the advantages associated with microreaction technology a series of SNAr reactions were performed under continuous flow by following previously developed microwave protocols as a starting point for the investigation. By this approach, an automated microreaction platform (Labtrix� S1) was employed for the continuous flow synthesis of diaryl ethers at 195 �C and 25 bar, affording a reduction in reaction time from tens of minutes to 60 s when compared with a stopped-flow microwave reactor.
Watts, Paul
Efficient continuous-flow synthesis of novel 1,2,3-triazole-substituted ?-aminocyclohexanecarboxylic acid derivatives with gram-scale production
Summary The preparation of novel multi-substituted 1,2,3-triazole-modified ?-aminocyclohexanecarboxylic acid derivatives in a simple and efficient continuous-flow procedure is reported. The 1,3-dipolar cycloaddition reactions were performed with copper powder as a readily accessible Cu(I) source. Initially, high reaction rates were achieved under high-pressure/high-temperature conditions. Subsequently, the reaction temperature was lowered to room temperature by the joint use of both basic and acidic additives to improve the safety of the synthesis, as azides were to be handled as unstable reactants. Scale-up experiments were also performed, which led to the achievement of gram-scale production in a safe and straightforward way. The obtained 1,2,3-triazole-substituted ?-aminocyclohexanecarboxylates can be regarded as interesting precursors for drugs with possible biological effects.
Otvos, Sandor B; Georgiades, Adam; Mandity, Istvan M; Kiss, Lorand
Translation of microwave methodology to continuous flow for the efficient synthesis of diaryl ethers via a base-mediated S(N)Ar reaction.
Whilst microwave heating has been widely demonstrated as a synthetically useful tool for rapid reaction screening, a microwave-absorbing solvent is often required in order to achieve efficient reactant heating. In comparison, microreactors can be readily heated and pressurised in order to "super-heat" the reaction mixture, meaning that microwave-transparent solvents can also be employed. To demonstrate the advantages associated with microreaction technology a series of S(N)Ar reactions were performed under continuous flow by following previously developed microwave protocols as a starting point for the investigation. By this approach, an automated microreaction platform (Labtrix(�) S1) was employed for the continuous flow synthesis of diaryl ethers at 195 �C and 25 bar, affording a reduction in reaction time from tens of minutes to 60 s when compared with a stopped-flow microwave reactor. PMID:22043247
Wiles, Charlotte; Watts, Paul
Synthesis of POSS-Based Ionic Conductors with Low Glass Transition Temperatures for Efficient Solid-State Dye-Sensitized Solar Cells.
Replacing liquid-state electrolytes with solid-state electrolytes has been proven to be an effective way to improve the durability of dye-sensitized solar cells (DSSCs). We report herein the synthesis of amorphous ionic conductors based on polyhedral oligomeric silsesquioxane (POSS) with low glass transition temperatures for solid-state DSSCs. As the ionic conductor is amorphous and in the elastomeric state at the operating temperature of DSSCs, good pore filling in the TiO2 film and good interfacial contact between the solid-state electrolyte and the TiO2 film can be guaranteed. When the POSS-based ionic conductor containing an allyl group is doped with only iodine as the solid-state electrolyte without any other additives, power conversion efficiency of 6.29% has been achieved with good long-term stability under one-sun soaking for 1000 h. PMID:24933357
Zhang, Wei; Wang, Zhong-Sheng
Efficient biocatalytic synthesis of (R)-[3,5-bis(trifluoromethyl)phenyl] ethanol by a newly isolated Trichoderma asperellum ZJPH0810 using dual cosubstrate: ethanol and glycerol.
(R)-[3,5-bis(trifluoromethyl)phenyl] ethanol is a crucial intermediate for the synthesis of Aprepitant. An efficient biocatalytic process for (R)-[3,5-bis(trifluoromethyl)phenyl] ethanol was developed via the asymmetric reduction of 3,5-bis(trifluoromethyl) acetophenone, catalyzed by whole cells of newly isolated Trichoderma asperellum ZJPH0810 using ethanol and glycerol as dual cosubstrate for cofactor recycling. A fungal strain ZJPH0810, showing asymmetric biocatalytic activity of 3,5-bis(trifluoromethyl) acetophenone to its corresponding (R)-[3,5-bis(trifluoromethyl)phenyl] ethanol, was isolated from a soil sample. Based on its morphological and physiological characteristics and internal transcribed spacer sequence, this isolate was identified as T. asperellum ZJPH0810, which afforded an NADH-dependent (R)-stereospecific carbonyl reductase and was a promising biocatalyst for the synthesis of (R)-[3,5-bis(trifluoromethyl)phenyl] ethanol. Some key reaction parameters involved in the bioreduction catalyzed by T. asperellum ZJPH0810 were subsequently optimized. The effectiveness of (R)-[3,5-bis(trifluoromethyl)phenyl] ethanol production was significantly enhanced by employing a novel dual cosubstrate-coupled system for cofactor recycling. The established efficient bioreduction system contained 50 mM of 3,5-bis(trifluoromethyl) acetophenone and 60 g l(-1) of resting cells, employing ethanol (6.0 %, v/v) and glycerol (0.5 %, v/v) as dual cosubstrate. The bioreduction was performed in distilled water medium, at 30 �C and 200 rpm. Under the above conditions, a best yield of 93.4 % was obtained, which is nearly a 3.5-fold increase in contrast to no addition of cosubstrate. The ee value of the product reached above 98 %. This biocatalytic process shows great potential in the production of (R)-[3,5-bis(trifluoromethyl)phenyl] ethanol, a valuable chiral building block in the pharmaceutical industry. PMID:23700239
Li, Jun; Wang, Pu; He, Jun-Yao; Huang, Jin; Tang, Jun
Deposition of Cryptosporidium parvum oocysts in porous media: a synthesis of attachment efficiencies measured under varying environmental conditions.
An extensive set of column experiments was performed with freshly harvested Cryptosporidium parvum oocysts to evaluate the effects of solution chemistry, surface coatings, interactions with other suspended particles, and pore fluid velocity on the fate and transport of this widely occurring waterborne pathogen in sandy porous media. We synthesized our data set with a comprehensive literature survey of similar experiments, to compute attachment (collision) efficiencies (?) used in colloid filtration theory (CFT) using three models for the single collector efficiency (?) across a wide range of experimental conditions. Most prior experiments have observed the transport of surface-treated, sterile C. parvum oocyst in porous media. Our column data confirm for freshly harvested oocysts that the presence of iron coatings on the sand medium and the presence of suspended illite clay drastically enhance oocyst deposition. Increasing ionic strength and decreasing pH also systematically enhance the attachment efficiency. Attachment efficiency decreases only at a very high ionic strength, most likely as a result of steric repulsion and possibly other changes in oocyst surface properties. Attachment efficiencies vary with fluid flow rate but without showing specific trends. We found that the computed attachment efficiency across all reported experiments could be reliably estimated using a regression model based on parameters related to ionic strength and pH. The regression model performed better with the Nelson-Ginn ? model and Tufenkji-Elimelech ? model than with the Rajagopalan-Tien ? model. When CFT is used in environmental assessments, the proposed regression model provides a practical estimator for attachment efficiencies of C. parvum oocyst deposition in porous media for a variety of environmental conditions unfavorable to attachment. PMID:22861686
Park, Yeonjeong; Atwill, E Robert; Hou, Lingling; Packman, Aaron I; Harter, Thomas
N,N-Diisopropyl-N-phosphonyl Imines Lead to Efficient Asymmetric Synthesis of Aziridine-2-Carboxylic Esters
Highly diastereoselective asymmetric synthesis of chiral aziridine-2-carboxylic esters is reported for 20 examples with good yields (51�87%) and excellent diastereoselectivities (>99:1 dr for most cases). The modified N-phosphonyl imines are proven to be superior to previous imine auxiliaries for the aza Darzens reaction by using secondary isopropyl to replace primary benzyl group for N,N-diamino protection. In the meanwhile, a special operation by slowly adding the pre-cooled imine solution at ?78 �C into the preformed ?-bromo lithium enolate mixture at this temperature in the presence of 4 � molecular sieves was found to be crucial in terms of yields and diastereoselectivity. The present method can provide an easy and general access to ?-hydroxy ?-amino acids and other important amino building blocks.
Kattamuri, Padmanabha V.; Xiong, Yiwen; Pan, Yi; Li, Guigen
Ultrasonic-assisted preparation of nano eggshell powder: a novel catalyst in green and high efficient synthesis of 2-aminochromenes.
The nano eggshell powder (NESP) has been prepared by ultrasound irradiation and used as a novel and biodegradable catalyst with high catalytic activity and reusability in green synthesis of 2-aminochromenes via condensation of ?- or ?-phathol, malononitrile and aromatic aldehydes at 120 �C under solvent-free conditions. The reaction proceeds to completion within 10-35 min in 91-98% yield. Nano eggshell catalyst was characterized by scanning electron microscopy, X-ray powder diffraction, IR spectroscopy and X-ray fluorescence, thermal gravimetric, surface area and elemental analyses. In addition, the catalytic activity and chemical structure of nano-sized eggshell were compared with pure CaCO3. PMID:23684545
Mosaddegh, Elaheh
In situ synthesis of CdS decorated titanate nanosheets with highly efficient visible-light-induced photoactivity
Appropriately dispersed CdS nanoparticles were intimately embedded into titanate nanosheets (TNS) through ion-exchange and in situ sulfurization process. The sheet-like intermediates of titanate during the transforming process into nanotubes were firstly used as substrate for the decoration of CdS nanoparticles, and the synthesis route was achieved by ion-exchange process between titanate precursor and Cd2+ ions solution, and the following sulfuration process by using Na2S solutions. The catalytic activity of the photocatalyst was investigated by photodegradation of Rhodamine B under visible light irradiation. With an optimal Cd/Ti molar ratio of 15%, the CdS/TNS composite exhibits the highest photocatalytic performance, which is approximately 5.4 times greater than that of pure TNS. The mechanism of the separation behavior of the photogenerated charges was also discussed.
Liu, Zhi; Fang, Pengfei; Liu, Fuwei; Zhang, Yupeng; Liu, Xinzhao; Lu, Dingze; Li, Delong; Wang, Shaojie
Nano scale magnetically recoverable supported heteropoly acid as an efficient catalyst for the synthesis of benzimidazole derivatives in water.
12-Tungstophosphoric acid supported on silica-coated magnetic nano particles was prepared and characterized by transmission electron microscopy, scanning electron microscopy, powder X-ray diffraction and inductively coupled plasma atomic emission spectroscopy. Acidity of the catalysts was measured by potentiometric titration with n-butylamine. Catalytic activity of the prepared sample was evaluated in the model synthesis of 1,2-disubstituted benzimidazole derivatives in water. The catalyst showed excellent catalytic activity and the corresponding products were obtained in good to excellent yields under mild reaction conditions. Furthermore, the catalyst could be easily recovered using an external magnet and reused several times. The leaching and surface acidity of the recovered catalyst were also investigated. PMID:24664342
Rafiee, Ezzat; Rahpeima, Nasibeh; Eavani, Sara
Efficient and green sonochemical synthesis of 3,3-bis(4-(dimethylamino)phenyl)indolin-2-ones.
A simple, green sonochemical synthesis of 3,3-bis(4-(dimethylamino)phenyl)indolin-2-ones, 2,2-bis(4-(dimethylamino)phenyl)-1H-indene-1,3(2H)-dione, 2,2-bis(4-(dimethylamino)phenyl)acenaphthylen-1(2H)-one and 5-(4-(dimethylamino)phenyl)-5-hydroxypyrimidine-2,4,6(1H,3H,5H)-triones using indium(III) chloride catalyst in aqueous media at room temperature is reported. Good yields, easy workup, short reaction time and the use of water as a solvent that is considered to be relatively environmentally benign are advantages of this new method. PMID:20843726
Khorrami, Afshin Rajabi; Faraji, Fereshteh; Bazgir, Ayoob
Synthesis of mono- and bisadducts of thieno-o-quinodimethane with C60 for efficient polymer solar cells.
A series of mono- and bisadducts of thieno-o-quinodimethane with C(60) (TOQC) was efficiently prepared through the Diels-Alder reaction of pristine or solubilizing side-chain-substituted 2,3-bis(chloromethyl)thiophene with C(60). The pristine TOQC bisadduct (bis-TOQC) shows much higher performance than the side-chain-substituted TOQC bisadducts in polymer solar cells, while the situation is inverse for the TOQC monoadducts. The best power conversion efficiency of 5.1% was achieved from the bis-TOQC:P3HT solar cells under simulated AM1.5G irradiation (86 mW/cm(2)). PMID:22360793
Zhang, Congyun; Chen, Shan; Xiao, Zuo; Zuo, Qiqun; Ding, Liming
Selectivity in Garratt-Braverman cyclization of aryl-/heteroaryl-substituted unsymmetrical bis-propargyl systems: formal synthesis of 7'-desmethylkealiiquinone.
Unsymmetrical bis-propargyl ethers and sulfonamides containing various combinations of aryl/heteroaryl substituents at the acetylene termini were synthesized, and their reactivity under basic conditions was studied. Moderate to high (chemo)selectivity was observed, which followed a trend opposite to that reported earlier for the corresponding sufones. The major products obtained in most cases (except with indole) were formed via participation of the heteroaryl ring or the less electron rich aryl ring. The selectivity observed in imidazole-based systems was exploited to complete a formal total synthesis of 7'-desmethylkealiiquinone, an analogue of the marine alkaloid kealiiquinone. PMID:24697833
Das, Joyee; Mukherjee, Raja; Basak, Amit
The economies of synthesis�
In this tutorial review the economies of synthesis are analysed from both detailed and macroscopic perspectives, using case-studies from complex molecule synthesis. Atom, step, and redox economy are more than philosophical constructs, but rather guidelines, which enable the synthetic chemist to design and execute an efficient synthesis. Students entering the field of synthesis might find this tutorial helpful for understanding the subtle differences between these economic principles and also see real-world situations where such principles are put into practice.
Newhouse, Timothy
N-aryl azacycloalkanes, an important class of building blocks in natural product and pharmaceuticals, are synthesized via an efficient and simple eco-friendly protocol that involves double N-alkylation of aniline derivatives. The reaction is accelerated by exposure to microwaves ...
Synthesis of L-Kedarosamine in Protected Form and Its Efficient Incorporation into an Advanced Intermediate to Kedarcidin Chromophore
An efficient route to the complex L-kedarosamine ?-glycosidic ether 2, a synthetic precursor to kedarcidin chromophore, is described. Central to the route, which is suitable for the preparation of multi-gram amounts of material, is a short synthetic sequence from D-threonine to protected L-kedarosamine derivatives and methodology for their ?-selective coupling with appropriate hydroxyl acceptors.
Ren, Feng; Hogan, Philip C.; Anderson, Alan J.; Myers, Andrew G.
In situ simultaneous synthesis of WC/graphitic carbon nanocomposite as a highly efficient catalyst support for DMFC.
WC/graphitic carbon nanocomposite was in situ simultaneously obtained from anion exchange resin-WO(4)(2-)-[Fe(CN)(6)](4-) complex, which could act as a highly efficient catalyst support for the direct methanol fuel cell. PMID:19462101
Wang, Ruihong; Tian, Chungui; Wang, Lei; Wang, Baoli; Zhang, Hengbin; Fu, Honggang
Facile synthesis of biocompatible cysteine-coated CuS nanoparticles with high photothermal conversion efficiency for cancer therapy.
The semiconductor compounds have been proven to be promising candidates as a new type of photothermal therapy agent, but unsatisfactory photothermal conversion efficiencies limit their widespread application in photothermal therapy (PTT). Herein, we synthesized cysteine-coated CuS nanoparticles (Cys-CuS NPs) as highly efficient PTT agents by a simple aqueous solution method. The Cys-CuS NPs have a good biocompatibility owing to their biocompatible cysteine coating and exhibit a strong absorption in the near-infrared region due to the localized surface plasma resonances of valence-band free carriers. The photothermal conversion efficiency of Cys-CuS NPs reaches 38.0%, which is much higher than that of the recently reported Cu9S5 and Cu2-xSe nanocrystals. More importantly, tumor growth can be efficiently inhibited in vivo by the fatal heat arising from the excellent photothermal effect of Cys-CuS NPs at a low concentration under the irradiation of a 980 nm laser with a safe power density of 0.72 W cm(-2). Therefore, the Cys-CuS NPs have great potential as ideal photothermal agents for cancer therapy. PMID:24950757
Liu, Xijian; Li, Bo; Fu, Fanfan; Xu, Kaibing; Zou, Rujia; Wang, Qian; Zhang, Bingjie; Chen, Zhigang; Hu, Junqing
Protein synthesis and degradation gene SNPs related to feed intake, feed efficiency, growth, and ultrasound carcass traits in Nellore cattle.
We looked for possible associations of SNPs in genes related to protein turnover, with growth, feed efficiency and carcass traits in feedlot Nellore cattle. Purebred Nellore bulls and steers (N = 290; 378 � 42 kg body weight, 23 months � 42 days old) were evaluated for daily feed intake, body weight gain (BWG), gross feed efficiency, feed conversion ratio, partial efficiency of growth, residual feed intake (RFI), ultrasound backfat, rump fat, and ribeye area. Genotypes were obtained for SNPs in the growth hormone receptor (GHR-1 and GHR-2); calpain (CAPN4751); calpastatin (UoGCAST); ubiquitin-conjugating enzyme 2I (UBE2I-1 and UBE2I-2); R3H domain containing 1 (R3HDM1-1, -2, -3, and -4), ring finger protein 19 (RNF19); proteasome 26S subunit, non-ATPase, 13 (PSMD13); ribosomal protein, large, P2 (RPLP2); and isoleucine-tRNA synthetase 2, mitochondrial (IARS2) genes. Allelic substitution, additive and dominant effects were tested and molecular breeding values were computed. CAPN4751, GHR-1 and -2, IARS2, R3HDM1-4, and UoGCAST were found to be normally segregating polymorphisms. Additive and dominance effects were observed on BWG, feed efficiency and carcass traits, although dominant effects predominated. Significant allelic substitution effects were observed for CAPN4751, GHR-1 and -2, and UoGCAST on BWG, gross feed efficiency, RFI, and carcass traits, under single- or multiple-marker analyses. Correlations between molecular breeding values and phenotypes were low, excepted for RFI, based on allelic substitution estimates obtained by stepwise linear regression. We conclude that SNPs in genes related to protein turnover are related to economically important traits in Nellore cattle. PMID:24065648
Gomes, R C; Silva, S L; Carvalho, M E; Rezende, F M; Pinto, L F B; Santana, M H A; Stella, T R; Meirelles, F V; Rossi J�nior, P; Leme, P R; Ferraz, J B S
Chemical Synthesis of Circular Proteins*
Circular proteins, once thought to be rare, are now commonly found in plants. Their chemical synthesis, once thought to be difficult, is now readily achievable. The enabling methodology is largely due to the advances in entropic chemical ligation to overcome the entropy barrier in coupling the N- and C-terminal ends of large peptide segments for either intermolecular ligation or intramolecular ligation in end-to-end cyclization. Key elements of an entropic chemical ligation consist of a chemoselective capture step merging the N and C termini as a covalently linked O/S-ester intermediate to permit the subsequent step of an intramolecular O/S-N acyl shift to form an amide. Many ligation methods exploit the supernucleophilicity of a thiol side chain at the N terminus for the capture reaction, which makes cysteine-rich peptides ideal candidates for the entropy-driven macrocyclization. Advances in desulfurization and modification of the thiol-containing amino acids at the ligation sites to other amino acids add extra dimensions to the entropy-driven ligation methods. This minireview describes recent advances of entropy-driven ligation to prepare circular proteins with or without a cysteinyl side chain.
Tam, James P.; Wong, Clarence T. T.
Protic acid immobilized on solid support as an extremely efficient recyclable catalyst system for a direct and atom economical esterification of carboxylic acids with alcohols.
A convenient and clean procedure of esterification is reported by direct condensation of equimolar amounts of carboxylic acids with alcohols catalyzed by an easy to prepare catalyst system of perchloric acid immobilized on silica gel (HClO(4)-SiO(2)). The direct condensation of aryl, heteroaryl, styryl, aryl alkyl, alkyl, cycloalkyl, and long-chain aliphatic carboxylic acids with primary/secondary alkyl/cycloalkyl, allyl, propargyl, and long-chain aliphatic alcohols has been achieved to afford the corresponding esters in excellent yields. Chiral alcohol and N-t-Boc protected chiral amino acid also resulted in ester formation with the representative carboxylic acid or alcohol without competitive N-t-Boc deprotection and detrimental effect on the optical purity of the product demonstrating the mildness and chemoselectivity of the procedure. The esters of long-chain (>C(10)) acids and alcohols are obtained in high yields. The catalyst is recovered and recycled without significant loss of activity. The industrial application of the esterification process is demonstrated by the synthesis of prodrugs of ibuprofen and a few commercial flavoring agents. Other protic acids such as H(2)SO(4), HBr, TfOH, HBF(4), and TFA that were adsorbed on silica gel were less effective compared to HClO(4)-SiO(2) following the order HClO(4)-SiO(2) > H(2)SO(4)-SiO(2) > HBr-SiO(2) > TfOH-SiO(2) > HBF(4)-SiO(2) approximately TFA-SiO(2). When HClO(4) was immobilized on other solid supports the catalytic efficiency followed the order HClO(4)-SiO(2) > HClO(4)-K10 > HClO(4)-Al(2)O(3) (neutral) > HClO(4)-Al(2)O(3) (acidic) > HClO(4)-Al(2)O(3) (basic). PMID:19618958
Chakraborti, Asit K; Singh, Bavneet; Chankeshwara, Sunay V; Patel, Alpesh R
Highly efficient synthesis and antitumor activity of monosaccharide saponins mimicking components of Chinese folk medicine Cordyceps sinensis.
Ergosterol 3-O-?-D-glucopyranoside (1a) and ergosterol 3-O-?-D-galactopyranoside (1b) were highly efficiently synthesized and evaluated for their inhibitory activities against two tumor cell lines. The structures of these compounds were extensively confirmed by (1)H, (13)C NMR, IR, and HRMS. Compounds 1a and 1b exhibited interesting cytotoxic profiles. The antitumor activity of compound 1a was higher than that of 1b. PMID:22428587
Zhu, Zhen-Yuan; Yao, Qiang; Liu, Yang; Si, Chuan-Ling; Chen, Jing; Liu, Nian; Lian, Hong-Yu; Ding, Li-Na; Zhang, Yong-Min
Ionic Liquid Promoted Eco-friendly and Efficient Synthesis of 2,3-Dihydroquinazolin-4(1 H )-ones
Summary.��2,3-Dihydroquinazolin-4(1H)-ones were efficiently synthesised by the reaction of isatoic anhydride, a primary amine or ammonium acetate, and different\\u000a aromatic aldehydes in 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim]BF4) without using any acidic catalyst. Also a bis-derivative of the title compound as a polyheterocyclic system was synthesised\\u000a successfully in high yield.
Minoo Dabiri; Peyman Salehi; Mostafa Baghbanzadeh
Copper (II) Schiff base catalysed aerobic oxidative coupling of 2-naphthols: an efficient and simple synthesis of binaphthols
Copper (II) Schiff base complexes of 2-(1-phenylethyl imino) methylphenol (3), methyl-N-(2-hydroxyphenyl)-l-serine (4) and methyl-N-(2-hydroxyphenyl)-l-tyrosine (5) were found to be an efficient catalyst for the aerobic oxidative coupling of 2-naphthols to binaphthols. Among the various copper (II) Schiff base complexes, the complex 3 was found to be the most reactive for this transformation.
Vishal B. Sharma; Suman L. Jain; Bir Sain
Copper-catalyzed double N-alkenylation of amides: an efficient synthesis of di- or trisubstituted N-acylpyrroles.
An efficient copper-catalyzed double alkenylation of amides with (1Z,3Z)-1,4-diiodo-1,3-dienes is reported for the first time. The reactions proceed to afford di- or trisubstituted N-acylpyrroles in good to excellent yields using CuI as the catalyst, Cs2CO3 as the base, and rac-trans-N,N'-dimethylcyclohexane-1,2-diamine as the ligand. PMID:17249731
Yuan, Xiyuan; Xu, Xiaobing; Zhou, Xiaobo; Yuan, Jiwei; Mai, Lugen; Li, Yanzhong
Gram-scale synthesis and efficient purification of 13C-labeled levoglucosan from 13C glucose.
(13)C-Labeled levoglucosan has been synthesized and purified in good yield, and on the gram scale in one step from commercially available (13)C glucose. This one-step protocol uses 2-chloro-1,3-dimethylimidazolinium chloride that serves to selectively activate the anomeric carbon toward substitution reactions. The labeled glucose is then smoothly converted to the anhydroglucose. Purification is efficiently achieved on large scale by chromatography on silica gel. PMID:24285138
Alexander, Lisa; Hoyt, Caroline; Michalczyk, Ryszard; Wu, Ruilian; Thorn, Dave L; Silks, L A Pete
Facile additive-free synthesis of iron oxide nanoparticles for efficient adsorptive removal of Congo red and Cr(VI)
The iron oxide nanoparticles had been successfully synthesized via an additive-free hydrolysis process at 75 �C for 12 h. The product was characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), and N2 adsorption-desorption. The results of XRD and N2 adsorption-desorption demonstrated that the as-prepared product was mainly ?-Fe2O3 with a large surface area of 164.1 m2 g-1. The TEM images illustrated that the as-prepared product was found to consist of a mixture of irregular spherical nanoparticles (a diameter of �50 nm) and nanowhiskers (a diameter of �50 nm and uneven length). The as-prepared product was used to investigate its promising applications in water treatment. Due to its small size and large surface area, the maximum adsorption capacities of Congo red and Cr(VI) have been determined using the Langmuir equation and found to reach up to 253.8 and 17.0 mg g-1, respectively. The facile synthesis method and the superior adsorption performance derived from the iron oxide nanoparticles display the potential applications for the removal of Congo red and Cr(VI) from aqueous solution.
Hao, Tao; Yang, Chao; Rao, Xuehui; Wang, Jide; Niu, Chunge; Su, Xintai
Synthesis of highly efficient antibacterial agent Ag doped ZnO nanorods: Structural, Raman and optical properties
Here, synthesis, structural, morphological, Raman, optical properties and antibacterial activity of undoped and Ag doped ZnO nanorods by chemical co-precipitation technique have been reported. Structural analysis has revealed that Ag doping cannot deteriorate the structure of ZnO and wurtzite phase is maintained. Lattice constants are found to be decreased with the Ag doping. Fourier transform infrared and Raman spectroscopy also confirm the X-ray diffraction results. Scanning electron microscopy results have demonstrated the formation of ZnO nanorods with average diameter and length of 96 nm and 700 nm, respectively. Raman spectroscopy results suggest that the Ag doping enhances the number of defects in ZnO crystal. It has been found from optical study that Ag doping results in positional shift of band edge absorption peak. This is attributed to the successful incorporation of Ag dopant into ZnO host matrix. The antibacterial activity of prepared nanorods has been determined by two different methods and compared to that of undoped ZnO nanorods. Ag doped ZnO nanorods exhibit excellent antibacterial activity as compared to that of undoped ZnO nanorods. This excellent antibacterial activity may be attributed to the presence of oxygen vacancies and Zn2+ interstitial defects. Our preliminary findings suggest that Ag doped ZnO nanorods can be used externally to control the spreading of infections related with tested bacterial strains.
Jan, Tariq; Iqbal, Javed; Ismail, Muhammad; Mahmood, Arshad
Efficient oxygen reduction electrocatalyst based on edge-nitrogen-rich graphene nanoplatelets: toward a large-scale synthesis.
The large-scale synthesis of nitrogen doped graphene (N-graphene) with high oxygen reduction reaction (ORR) performance has received a lot of attention recently. In this work, we have developed a facile and economical procedure for mass production of edge-nitrogen-rich graphene nanoplatelets (ENR-GNPs) by a combined process of ball milling of graphite powder (GP) in the presence of melamine and subsequent heat treatment. It is found that the ball milling process can not only crack and exfoliate pristine GP into edge-expanded nanoplatelets but also mechanically activate GP to generate appropriate locations for N-doping. Analysis results indicate that the doped N atoms mainly locate on the edge of the graphitic matrix, which contains ca. 3.1 at.% nitrogen content and can be well-dispersed in aqueous to form multilayer nanoplatelets. The as-prepared ENR-GNPs electrocatalyst exhibits highly electrocatalytic activity for ORR due to the synergetic effects of edge-N-doping and nanosized platelets. Besides, the stability and methanol tolerance of ENR-GNPs are superior to that of the commercial Pt/C catalyst, which makes the nanoplatelets a promising candidate for fuel cell cathode catalysts. The present approach opens up the possibility for simple and mass production of N-graphene based electrocatalysts in practice. PMID:24598249
Fu, Xiaogang; Jin, Jutao; Liu, Yanru; Wei, Zhiyang; Pan, Fuping; Zhang, Junyan
Synthesis of ?-cyclodextrin/chitosan composites for the efficient removal of Cd(II) from aqueous solution.
The synthesis of chitosan-graft-?-cyclodextrin (Ch-g-?-CD) using persulfate/ascorbic acid redox system was done and characterized by FTIR, XRD, TGA and SEM/EDX. The optimum yield of the copolymer was obtained using 16�10(-3) M ?-cyclodextrins (?-CD), 2.8�10(-2) M ascorbic acid (AA), 1.8�10(-2) M K(2)S(2)O(8) and 0.1g chitosan in 25 mL of 2% aqueous formic acid at 45�0.2�C. The highest percent grafting samples were evaluated for cadmium metal ion (Cd(II)) removal from the aqueous solutions where the sorption capacities were found proportional to the grafting extent. The sorption was pH and concentration dependent where, pH=8.5 was found to be the optimum value. The adsorption data were modeled using Langmuir and Freundlich isotherms. The equilibrium data followed the Langmuir isotherm model with maximum sorption capacity of 833.33 mg/g. The influence of electrolytes, sodium chloride (NaCl) and sodium sulphate (Na(2)SO(4)) on Cd(II) uptake was also studied. Desorption of the cadmium loaded Ch-g-?-CD was accomplished with 0.01 N H(2)SO(4). The adsorbent exhibited high reusability and could be successfully recycled for nine cycles where in the ninth cycle 27% adsorption was feasible. PMID:21689680
Mishra, A K; Sharma, A K
Solvothermal synthesis of InP quantum dots and their enhanced luminescent efficiency by post-synthetic treatments.
InP quantum dots (QDs) were solvothermally synthesized by using a greener phosphorus source of P(N(CH(3))(2))(3) instead of highly toxic P(TMS)(3) widely used, and subsequently subjected to a size-sorting processing. While as-grown QDs showed an undetectably low emission intensity, post-synthetic treatments such as photo-etching, photo-radiation, and photo-assisted ZnS shell coating gave rise to a substantial increase in emission efficiency due to the effective removal and passivation of surface states. The emission efficiency of the photo-etched QDs was further enhanced by a consecutive UV photo-radiation, attributable to the photo-oxidation at QD surface. Furthermore, a relatively thick ZnS shell on the surface of InP QDs that were surface-modified with hydrophilic ligands beforehand was photochemically generated in an aqueous solution at room temperature. The resulting InP/ZnS core/shell QDs, emitting from blue to red wavelengths, were more efficient than the above photo-treated InP QDs, and their luminescent properties (emission bandwidth and quantum yield) were comparable to those of InP QDs synthesized with P(TMS)(3). Structural, size, and compositional analyses on InP/ZnS QDs were also conducted to elucidate their core/shell structure. PMID:21194707
Byun, Ho-June; Lee, Ju Chul; Yang, Heesun
Synthesis and evaluation of diethylethylamine-chitosan for gene delivery: composition effects on the in vitro transfection efficiency.
Chitosan has been indicated as a safe and promising polycation vector for gene delivery. However its low transfection efficiency has been a challenging obstacle for its application. To address this limitation, we synthesized chitosan derivatives which had increasing amounts of diethylethylamine groups (DEAE) attached to the chitosan main chain. The plasmid DNA VR1412 (pDNA), encoding the �-galactosidase (�-gal) reporter gene was used to prepare nanoparticles with the chitosan derivatives, and the transfection studies were performed with HeLa cells. By means of dynamic light scattering and zeta potential measurements, it was shown that diethylethylamine-chitosan derivatives (DEAE(x)-CH) were able to condense DNA into small particles having a surface charge depending on the polymer/DNA ratio (N/P ratio). Nanoparticles prepared with derivatives containing 15 and 25% of DEAE groups (DEAE(15)-CH and DEAE(25)-CH) exhibited transfection efficiencies ten times higher than that observed with deacetylated chitosan (CH). For derivatives with higher degrees of substitution (DS), transfection efficiency decreased. The most effective carriers showed low cytotoxicity and good transfection activities at low charge ratios (N/P). Vectors with low DS were easily degraded in the presence of lysozyme at physiological conditions in vitro and the nontoxicity displayed by these vectors opens up new opportunities in the design of DEAE-chitosan-based nanoparticles for gene delivery. PMID:23306549
de Paula Pansani Oliveira, Franciele; Dalla Picola, Isadora Pfeifer; Shi, Qin; Barbosa, Hellen Franciane Gon�alves; Tiera, Vera Aparecida de Oliveira; Fernandes, J�lio Cesar; Tiera, Marcio Jos�
Efficient synthesis of D-branched-chain amino acids and their labeled compounds with stable isotopes using D-amino acid dehydrogenase.
D-Branched-chain amino acids (D-BCAAs) such as D-leucine, D-isoleucine, and D-valine are known to be peptide antibiotic intermediates and to exhibit a variety of bioactivities. Consequently, much effort is going into achieving simple stereospecific synthesis of D-BCAAs, especially analogs labeled with stable isotopes. Up to now, however, no effective method has been reported. Here, we report the establishment of an efficient system for enantioselective synthesis of D-BCAAs and production of D-BCAAs labeled with stable isotopes. This system is based on two thermostable enzymes: D-amino acid dehydrogenase, catalyzing NADPH-dependent enantioselective amination of 2-oxo acids to produce the corresponding D-amino acids, and glucose dehydrogenase, catalyzing NADPH regeneration from NADP(+) and D-glucose. After incubation with the enzymes for 2�h at 65�C and pH�10.5, 2-oxo-4-methylvaleric acid was converted to D-leucine with an excellent yield (>99�%) and optical purity (>99�%). Using this system, we produced five different D-BCAAs labeled with stable isotopes: D-[1-(13)C,(15)N]leucine, D-[1-(13)C]leucine, D-[(15)N]leucine, D-[(15)N]isoleucine, and D-[(15)N]valine. The structure of each labeled D-amino acid was confirmed using time-of-flight mass spectrometry and nuclear magnetic resonance analysis. These analyses confirmed that the developed system was highly useful for production of D-BCAAs labeled with stable isotopes, making this the first reported enzymatic production of D-BCAAs labeled with stable isotopes. Our findings facilitate tracer studies investigating D-BCAAs and their derivatives. PMID:23661083
Akita, Hironaga; Suzuki, Hirokazu; Doi, Katsumi; Ohshima, Toshihisa
Pd(OAc)2/DABCO as an efficient and phosphine-free catalytic system for the synthesis of single and double Weinreb amides by the aminocarbonylation of aryl iodides.
This work reports a mild, stable and efficient Pd(OAc)2/DABCO catalysed protocol for the synthesis of single and double Weinreb amides. Double Weinreb amides, having 1,4-phenylene- and biphenylene-linkers - important backbones for the synthesis of biologically active symmetrical resorcylate oligomer units - were synthesized by the double carbonylation of aryl diiodides. Notably, the reaction does not require any expensive or air/moisture sensitive phosphine ligands. DABCO was found to be an inexpensive and stable ligand for the Pd(OAc)2 catalysed carbonylation of aryl iodides under an atmospheric pressure of carbon monoxide, and offered excellent yields of the single and double Weinreb amides. PMID:24967832
Gadge, Sandip T; Bhanage, Bhalchandra M
Superparamagnetic plasmonic nanohybrids: shape-controlled synthesis, TEM-induced structure evolution, and efficient sunlight-driven inactivation of bacteria.
Magnetic materials and noble metal-based multifunctional hybrids have attracted much attention recently due to their unique properties and potential applications in a variety of fields. However, substantial challenges remain to directly obtain water-soluble hybrids with well-defined structures and to directly combine magnetic nanoparticles with nonspherical noble metals. We describe here for the first time a simple solvothermal method to synthesize a series of novel water-soluble nanohybrids composed of shape-tuned Ag cores and a Fe(3)O(4) shell. We found that small Fe(3)O(4) grains can be well-distributed directly on the surface on the Ag seeds. Such hybrids have both plasmonic and significant superparamagnetic properties, enabling magnetic separation. The plasmon resonance frequency of Ag nanostructures can be fine-tuned through the interactions between the two components. In addition, the decorated Fe(3)O(4) nanoparticles stabilized the Ag nanostructures when exposed to air and natural light for a long time. Furthermore, an interesting structural transformation is observed in the one-dimensional Ag-Fe(3)O(4) nanowires under high-energy electron beam. The Ag core can diffuse through the porous iron oxide shell, break away, and result in the formation of Ag nanocluster-decorated iron oxide tubes. Finally, the hybrids acted as a chemical template for the synthesis of Fe(3)O(4)/Au-AgCl double-layer nanotubes that display obvious near-infrared absorption. Importantly, the double-layer nanotubes exhibited enhanced photocatalytic inactivation of bacteria at very low co