kedarsidin

cadersidine heey eka chromoprotein antitumer pratijaivik aahe, jeey pratham 1992 madhye actinomycetpasoon vegale kele gele, jyat eka ensa-sankarit anidine chromophore (darshavilele) tasech eka apoprotein aahe jeey actinomycetmadhil vish sthir karnyas madat karate. done alkinyl upanganshi thet jodalelya alken asalelya nauu-kinwa-daha-sadasyanchya gabha sanrachanesathi naav dilelya aushadhanchya anidine vargachya itar sadasyanpramanech-utpadak jivanshi spardha vapar jivanunna marnyasathi cadersidine bahudha vikasit jhaale hote. kaaran teey dii. aine. aii. chey nuksan karoon heey sadhya karate, tathapi, cadersidine arbud peshinna dekhil haanee pohochavanyas saksham aahe. asha prakare cadersidine haah tyachya sanrachanatmak guntaguntisathi tasech karkarogvirodhi gunadharmansathi vaidnyanik sanshodhanacha vishay aahe.
shodh aanee rachana spashtikaran.
cadersidinecha shodh pahilyanda 1992 madhye lagla jevha bristol-myers squib yethe kelelya jaiv-parikshananni actinomycet strainchya kinwan matanachya madhye dii. aine. aii.-hanikarak chromoproteinchi upasthiti darshavili. yuu. vhee. spectroscopidware naun-peptidic chromoforecha sahbhag nishchit keela gela aanee yaa noncovalentally bound chromophorela tyachya apoprotein hostpasoon vegale karnyasathi reverse-fages chromatography vapar keela gela. heey vilag-cadersidine chromophore-sabhovatalachya paristhitit sahaj vighatit hote aanee tyat cytotoxicity (aay. see. 50.0.40 enji/miilii, etch. see. tii.-116 manvi colorectal carcinoma peshi resha) asalyache disun aale.
tyanantarchya aine. emm. aar., maas spectrometry, rasayanik apghatan aanee vyutpatti prayoganmule vilgikaran pathkala kedarsidine chromophorechi pramukh sanrachanatmak vaishishtye olakhata aalee, jyat anidine cyclic coor, ensa-sanyugma chloropyridyl ring, micross aanee kedarosamine sakhar aanee naphthomide parishisht yancha samavesh aahe. tathapi, guntaguntichya sanrachanemule udbhavalelya aavhananmule, prarambhik ahavalat anek truti hotya. bicyclic korche vighatan karane visheshtah katheen tharale, kaaran noee sahsambandhanchya vyakhyemule sanshodhakanni coor stereotetradechya sapeksh stereochemistrychi chukichi rachana kelee. shivay, jaagtik nirpeksh rasayanshastra heey stereodifiened-micherose sakhar aanee aglycone yanchyatil noee parasparsambandhanchya aadhare niyukt kele gele hote, stereotetradechya truti eglaikonchya itar done stereocentermadhye pasarlya. naphthomide samoohacha 'ansa' pulashi sampark dekhil prarambhik ahavalat chukicha tharvanyat aala.
nantar tohoku vidyapith aanee harvard vidyapithatil sanshodhakanchya swatantra krutrim prayatnandvare yaa truti durust karnyat aalya. 1997 madhye, mool nondavalelya sanrachanechya margavar, masahiro hiramachya nirdeshakhali sanshodhakanna asey aadhalale qee prastavit chloroazaterosyl ("s")-α-emino acid vyutpannacha spectroscopic deta, 'leat' aanee itar 'dware darshavilelya ksharan utpadanashi susangat navhata. tyaeivaji, hirama gatane eka ("aar")-beeta-amino aaml vyutpann prastavit aanee pramanit kele. yaa punaravaloknamule hirama 'ett all' jhaala. itar aglycone stereocenter dekhil ulat karnyasathi, kedarsidin chromophorechi sudharit rachana pradan karnyasathi jee keval micarose-vahak carbon, see 10 chya sapeksh stereochemistrymadhye bhinn hotee. shevati, 2007 madhye, myers aanee aanee hirama "ett all" neey prastavit kelelya sanrachaneche sanshleshan kele.sambandhit aine. emm. aar. spectroscopic deta naisargik utpadanapeksha vegala hota, jyamule myers gatane micarose-dharan vapar carbonchya stereochemistrymadhye 10 ("s") paryant sudharana kelee.
krutichi yantrana.
itar enidinpramanech, cadersidine chromophoremadhye eka mukhya rachana asate jee vidhvansak mukt radicals tayar karate, tasech heey 'warhead' tyachya dna lakshyaparyant pohochavinare upang asatat. asha prakare, cadersidine chromophore jyaa samanya yantranedvare dii. aine. aii. laa haanee pohochavate tee samanya yantrana dnyat aahe; tathapi, yaa prakriyeche tapasheel-visheshtah nucleophilic sakriyatechi aavashyakta-vadgrast aahet.
mukt-radical dii. aine. aii. chey nuksan.
serve anidine pratijaivikanmadhye jaivprakriyashilata ektrikaran karnari yantrana mhanje bergman cyclisation, jyamadhye anidine bhagala utsfurt cycloaromatisationmoodhun jaave lagate aanee yogya datyankadun hydrogenchya samarupi amurtatesathi sakriy kelele "parra"-benzine biradical tayar hote, jyat dii. aine. aii. chya deoxyribose sharkarancha samavesh asato. yamule dii. aine. aii. varr carbon-kendrit mukt mooldrav tayar hote, jeey aanvik auksijandware auxidation hote. parinami peroxideche vighatan houn dii. aine. aii. madhye eka kinwa done-fase asalele vikhand tayar hotat, jyamule shevati peshi maran pavtat.
lakshaniy anukram nivadaktasah, kedarsidin chromophore tii. see. see. tii. aine.-merchya thikani dii. aine. aii. laa pradhanyane bandhato aanee too todato, jyamule ekeri-pattyache viram tayar hotat. gondhalat takanare, cadersidine chromophorechi rachana neocarginostatin chromophoreshy sarvat jawalun sambandhit asali taree, pahili sanrachanatmakdrushtya vegali calichemacin endien antitumer pratijaivikasaha anukram-vishishtata samayik karate. naphthoic acidchi sanrachana dii. aine. aii. bandhanimadhye samavisht kelee gelee aahe, bahudha intercalationdware. yasathi, cadersidine chromophore-prerit dii. aine. aii. chee vighatana, see. aii. 2 + aanee emm. jee. 2 + sarkhya dvimiteey catayanchya jodanimule qamee hote, jeey cadersidine chromophorechya naphthoic acid gatala chilletively bandhatat aanee asha prakare dii. aine. aii. sathiche tyache aakarshan qamee karatat. dii. aine. aii. kirkol khambache dnyat bandhak, netropsins spardha prayog, asey soochit karatat qee kedarsidin bahudha lahan khamb dekhil bandhato.
nucleophilic sakriyakaran.
"inn vivo" madhye madhye madhye thioletschee neucellophilic bharr aanee parinami coor epoxide ughadane heey cadersidine chromophoremadhye bergman cyclisationla chalana denyasathi gruheet dharale gele aahe. nucleophilic sakriyatemule cycloaromatised utpadanachya nirmitimule ring strain qamee hoto aanee asha prakare dii. aine. aii. skishanakade cadersidine chromophore sakriy hoto asey manale jaate. leet "ett all" dware kelelya vilgikaran aanee sanrachanatmak vaishishtyikaran abhyasanmadhye., cadersidine chromophorechya chromophorechya borohydride qamee honyamule jalad cycloaromatisation prerit jhaale aanee tyamule anyatha asthir naisargik utpadanacha abhyas sulabh jhaala. parinami, 'inn vivo' yaa cycloaromatisation ghatanela chalana denyasathi sambhavya sadhan mhanoon punaravalokan sahityat sahityat sakriyatecha vyapakpane prastav aahe.
alikadil purave asey suchavatat qee cadersidine chromoforeche utsfurt cycloaromatisation heey 'inn vivo' hii pramukh yantrana naslyas, nucleophilic bioactiviationshy spardhatmak aahe. tarr tarr gananevarun asey disun yete qee cyclic koarmadhil koarmadhil duheri bandh mothya pramanat ring strain (see. aii.) pradan karato. 14 kcal·mol−1) teey [6,5,5] bergman cyclisation-reduction, hirama "ityadivar tayar jhalelya tricycle."lakshat ghya qee 5,9-fused anidine coer thayol" "sakriy karnare ghatak" "aanee (naun-solvent) hydrogen datyanchya anupasthitit cycloaromatisation-reductionsathi sanvedanshil aahe". cadersidine chromophore eglaykonmadhye samaan ritine β-mercaptoethanol yaa samanya thayol reductantchya upasthitichi parva naan karata tulanatmak darane reductive cycloaromatisation hote. eka pratikruti pranalimadhye asey aadhalun aale qee cadersidine chromoforecha 5,9-chakriy gabha sambandhit 5,5,6-tricyclic cycloaromatised byradicalshi samtol sadhat aahe. yaa pratimanatil anidianchya chhadm-pratham-kramachya kshay darr haah dravak hydrogen-daata kshamatevar atyant avalambun asato, jeey soochit karate qee dvidhruviy nirmitinantar hydrogen amurtata payari, dvidhruviy pranalichya ulat, anidianchya cycloaromatisation gatimandrushtya mahattvapoorn aahe, jithe dvidhruviy nirmiti swatach darr-maryadit karnari payari mhanoon olakhali jaate. heey lakshat ghenyasarkhe aahe qee tapasalelya dravkanpaiki, tetrahydropheuran-sanrachanatmakdrushtya deoxyriboses samaroop-yamule 5,9-fused anidian scaffold ("tii" 1⁄2 = 68 minit); zeane "aanee itaranche tulanene jalad vighatan jhaale."swatantrapane tippani qaraa qee deoxyribose 4 '-hydrogen amurtata bahudha cadersidine chromophore jaiv sakriyatemadhye karyarat aahe.
epi-kedarsidine chromoforeche sanshleshan.
2007 madhye, harvard vidyapithatil myers aanee aanee qee-epee-kedarsidine chromophorechya sanshleshanachi nond kelee, jee 1997 madhye hirama "ett all" neey vikasit kelelya sudharit sanrachaneshi sambandhit hotee. yaa prayatnachya yashasathi mahattvapoorn asalele purvasanshleshit vishleshan hote, jeey andaje samaan rasayanik guntagunti asalelya ghatakanchya abhisaran jodanivar kendrit hote. qee-epee-kedarsidine chromophorechi anek pramukh aavhane, tasech yaa adchaninche nirakaran karnyasathi vaparlya jaanarya dhorananvar khalee charcha kelee aahe.
anidine anidine antarnihit asthirata.
bergmanchya chakrakar-ghat vighatan marganprati asthirata, anidineschya konatyahi prastavit sanshleshanasathi motha dhoka nirman karate. myers aanee sahkari heey dayitva olephinachya shevatchya tappyatil nirjalikaran pratishthapanadvare hatalatat. done alkinyl pulanna pulanna yaa asantruptishivay, krutrim madhyavarti padarthancha bergman-prakarchya vighatanakade vilhewat lavali jaat nahee aanee vighatan honyacha dhoka qamee hoto. yaa prakaranat, martin sulfuranechya upcharandvare propargilic alcoholche nirjalikaran prerit kele gele.
epoxide stereochemistry.
10-epee-kedarsidine chromophore, myers aanee itaranna lakshya karnyat. epoxide karyakshamta sanlagn qee hydroxyl gatamadhye sthapit karnyacha prayatna keela. qee hydroxyl gatadware nirdeshit vandium-utprerit epoxidationdware heey sadhya jhaale. naisargik qee-("ess")-epimer ichchit asalyas, heey kalpana karnyayogya aahe qee qee hydroxylchya trialkilsilil sanrakshanamule olephinachya β facechya steric auklujandware ichchit α-faces epoxidation utpadan hoil; tathapi, proximal alkinchya auxidationla gatee denyasathi nirdesh gatavina, yaa kalpanik pratikriyes kadachit kharab regioselectivitycha tras hoil, kaaran renumadhil itar see-see asantruptinche auxidation ichchit pratikriyeshi spardha karel.
cyclechya gabhache bandhkam.
myers aanee aanee cadersidine chromophore aanee neocarginostatin chromophorechya 5,9-fuse kelelya cyclic koarchya sanshleshanat transanular ionic cyclisation pratikriyanchya vaparat pudhakar ghetala aahe. pahilya avtarat, chakriy tetrinela hydride vitaran heey aluminiumchya samanvayadvare nikatvarti alcoxideshy nirdeshit kele gele hote, asha prakare salag done 5-exo-digg-prakarchya chakranandware eka tappyat ichchit anidine gabha tayar keela gela. koarche nantarchya pidhitil sanshleshan heey zaranyache chakrantar rokhate, chakriy vinail bromidever lithiyam-halogenchya devanghevanivar avalambun rahoon chakriy utpadanasathi vinail aayan purvavarti tayar karate.
qee-epee-kedarsidine chromoforecha chakriy gabha vareel purvasanshleshit yojnabaddha swarupat darshavilyapramane, carbon-carbon bandh tayar vapar teen pratikriyanchya anukramik vaparadvare tayar keela gela. pratham, bromovinil electrophile aanee alkynyl nucleophile yanchyat sonogashira jodani karnyat aalee; tyanantar done antim alkinechya glazer jodanidware chakriy trian denyasathi ring closure purn karnyat aale. 5, 9-fuse kelele cycle kendra heey vinilithium prajatichya 'inn seatoo' pidhidware sthapit kele gele hote, jyache transanular 5-exo-digg cyclisation jhaale hote.
ensa-sankarit macrolectone.
sheena macrolectonizationcha vapar karoon pahilya sonogashira jodaninantar ensa-sanyugma macrolectone tayar karnyat aale. intramolecular esterificationla protsahan denyasathi 2-methyl-6-nitrobenzoic enhydride, 4-dimethylaminopyridine aanee triathylamine aadhar mhanoon vapar karoon tyache utpadan qamee naan karata haah protocol graam-scalever keela gela.
jaivasanshleshan.
jyaa madhyamandvare jivanu kedarsidinsarkhe anidine tayar karatat teey sanshodhanala prerit karat rahatat. cadersidine chromophore, too itar anidines samayik karato tyaa carbocyclic koarchya palikade, atirikt jaivasanshleshit kodee sadar karatoh cadersidine comoforechya carbocyclic coerla jodalelya gatanchi sapeksh stereochemistry jawalun sambandhit anidinespeksha vegali aahe; ("aar")-2-eza-3-chloro-beeta-tyrosine substructure itar konatyahi dnyat naisargik utpadanat olakhale gele nahee; aanee tyache sadhepana disat asoonahi, naphthonet samoohachya isopropoxy pratisthapanchya jaivasanshleshanasathi sahitya pradhanya qamee aahe.
anidine tayar karnyasathi jababdar asalelya jaivik yantrasamagriche sanketan vapar jaivasanshleshit januk samoohanche pratirupan kele gele aahe aanee tyanche vaishishtya mhanje paach 9-sadasyanchi anidine (see-1027, neocarginostatin, maduropeptin, sporolides aanee kedarsidine) aanee teen 10-sadasyanchi anidine (calichemacin, asperamacin aanee dynamikine). yaa jaivasanshleshit upkarananchya tulanatmak abhyasatoon asey disun aale aahe qee yaa renuncha anidine gabha, anidine polycatide synthes (pii. keey. ess.) yaa samanya enzymedware suru keela jaato. yaa enzymeche polyane utpadan nantar upasthit asalelya vishisht pii. keey. ess.-sambandhit enzymesnusar anidinechya 9 kinwa 10 sadasyanchya kormadhye bhinn prakare vistrut kele jaate. tyanantar utpadak jivandware eka abhisari jaivasanshleshi dhoran vaparale jaate, jyamadhye antim utpadan denyasathi anidineche vegvegale paridhiy parishisht mukhya sanrachaneshi jodale jaatat.
2013 madhye, scrips sanshodhan sanstha aanee wisconsin-maddison vidyapithatil sanshodhakanni cadersidine biosynthetic clusterche ("keey. dii.") yashasvi cloning aanee vaishishtyikaran nondavale. yaa pratirupit januk samoohachya olakhichi pushti 'keda' yaa samoohatil janukadware kelee gelee, jeey purvi vegale kelele cadersidine apoprotein, tasech 'kede' aanee 'kede 10', jyachi saha-abhivyakti 'eae' madhye aahe, tyanna kootbaddha karate. kolaimule 'heptin' heey purvichya endean coor jaivasanshleshanat samavisht asalele eka vishisht utpadan tayar jhaale.
cadersidine chromoforeche 2-azah-beeta-tyrosine upghatak itar konatyahi naisargik utpadanat purnapane adnyat aahe; pradhanyacha haah abhav yaa sanrachanechya sanshleshanasathi jababdar asalelya janukanchi "prayori" olakh karnyachya konatyahi prayatnala nirash karato. tathapi, cadersidine, see-1027 aanee maduropeptin jaivasanshleshit samoohanmadhye sahaa januke sanrakshit kelee jaatat-yaa nantarchya done anidinemadhye 2-azah-beeta-tyrosine upghatak nasato, tarr tyanchyat samaan ()-tyrosine-vyutpann ghatak asatat, jeey pramukh kombadi aanee itar asatat."2-azah-tyrosynpasoon suru suru sambandhit cadersidine upghatak sanshleshanasathi eka marg prastavit karane. asha prakare heey α-amino aaml, "caid" samoohamadhye encode kelele aminomutage, aminomutage dware sambandhit β-amino aamlat rupantarit kele jaate asey manale jaate. parinami utpadan peptidial vahak prathin prathin varr bharalele asalyache manale jaate aanee tyanantar flavin edenine dynucleotide-aadharit halogeness, halogeness dware chlorinate kele jaate.
isopropoxy-2-naphthonet upanganchya jaivasanshleshanachi antardrushti, anukrame naphthonet kinwa benzoate ghatkansah endean asalelya neocarginostatin aanee maduropeptin 'caid' samoohanchya tulanatmak vishleshanadvare prapt jhaali. paach januke, keey. dii. aine. 1-aine. 5, neocarginostatinmadhe naphthonet sanshleshanasathi jababdar asalelya enzymes uchch anukram samarupata dharan karatat-parinami, cadersidine jaivasanshleshanat 3,6,8-trihydroxy-2-naphthoic acidchi madhyasthata prastavit kelee jaate. heey sanyug 3,6,7,8-tetrahydroxy vyutpannamadhye oxygenyukt asalyache manale jaate, nantar keey. dii. aine. 1, eka "oo"-methyltransferagedware teen vela "oo"-methylayukt kele jaate. ananya isopropoxy paryay, shenn aanee itar pradan karnyasathi."radical samm methyltransferase keey. dii. aine. 5 dware sambandhit methoxy gatache duheri" see "-methylation qaraa.
nishkarsh.
tyachya vishisht nasalelya cytotoxicitymule, sabhovatalachya paristhitit asthirata aanee vilgikaran aanee utpadanachya sapeksh kharchamule, cadersidine chromophorechi upcharatmak umedvar mhanoon sakhol tapasani kelee gelee nahee. tathapi, varr charcha kelelya alikadil vaidnyanik pragatimule haah shevatcha adthala qamee honyas madat jhaali aahe, kaaran scalable cadersidine utpadanachya dishene purnapane krutrim aanee jaivasanshleshit marg aata pohochanyachya aat aahet. shivay, pratipinde-aushadh sanyugmit upcharanchya vadhatya lokpriyatemule, yaa shaktishali cytotoxine lakshyit vitaranadvare visharipanache dayitva qamee kele jaau shakate, jyamule yaa guntaguntichya samagricha kiman pramanat vapar vapar karyaksham upcharanna saksham karata yete. naun-hodgkin lymphomachya upcharasathi calichemacin-aadharit pratipinde-aushadh sanyugmit innotuzumab ozogamicincha alikadil vikas, manvi rogachya upcharanmadhye gambhir vapar shodhanyasathi anidinechi kshamata majboot karato. asha prakare, cadersidinechi jaivik kshamata aanee guntaguntichi aanvik rachana yaa padarthachya pudhil vaidnyanik chaukashila prerana deu shakate aanee karkarogaviruddhachya yuddhat kadachit naveen shastrastra pradan karoo shakate.

