 derivative of castor oil, Cremophor EL(copyright) and ethanol (50:50) because of its lack of significant aqueous or liposome solubility. However, the Cremophor EL(copyright) carrier itself can cause toxic side effects or increase the side effects caused by the taxane when administered to animals. Thus, administration of the Cremophor EL(copyright): ethanol -based paclitaxel formulation generally entails premedication with other drugs, as well as a slow infusion of a large volume of the formulation, thus often necessitating over night hospital stays and their attendant costs. Alternatively, a stable formulation of a taxane with a lower concentration of a polyoxyethylated derivative of castor oil could be important in reducing the toxic side effects of the drug product.
Compositions provided herein provide taxanes in the form of compounds which are taxanes to which an acyl chain has been attached. The acyl chain enhances the taxane""s lipid solubility. Thus, the taxane can be stably associated with a lipid-based carrier such as a liposome, for an extended period of time. However, the compositions provided herein may also be administered in non-liposomal carriers, such as USP/NF Polyoxyl 35 Castor Oil. The acyl chain itself has been derivatized by the attachment thereto of a hydrolysis-promoting group, which is a chemical moiety that promotes hydrolysis of the derivatized acyl chain from the parent taxane, once the taxane has been disassociated from the lipid-based carrier, so as to give the parent taxane in a therapeutically useful form. The hydrolysis-promoting group may take the structure of a single enantiomer or may be administered as a mixture of (S) and (R) enantiomers. There may be a stereospecific difference in the biological and pharmacological activity attributable to the enantiomeric form. While not being limited to this explanation, it is possible that in vivo cleavage may favor one enantiomer. Thus, by providing a method to deliver the preferred enantiomeric form of the hydrolyzable hydrophobic taxane of the present invention, administeration of lower dosage than with mixed racemic forms may provide equivalent therapeutic effect. The present invention, therefore, additionally provides methods for preparing single enantiomeric forms of the hydrolyzable hydrophobic acyl chains and methods for synthesizing the hydrolyzable hydrophobic taxane having a single enantiomeric substituted fatty acid or at least enriched in a single enantiomeric form.
The compounds provided
derivative of castor oil, Cremophor EL(copyright) and ethanol (50:50) because of its lack of meaning aqueous or liposome solvability. However, the Cremophor EL(copyright) aircraft carrier itself can cause toxic side impression or increase the side effects induce by the taxane when administer to animals. therefore, presidency of the Cremophor EL(copyright ): ethanol -based paclitaxel conceptualization generally entails premedication with other drugs, equally well as a slow infusion of a large bulk of the formulation, thus frequently necessitating over night hospital stays and their attendant price. Alternatively, a stable formulation of a taxane with a lower assiduity of a polyoxyethylated derivative of caster oil could be important in reducing the toxic english effects of the drug product. 
 Compositions provided herein provide taxanes in the mannequin of compounds which are taxanes to which an acyl chain has been attached. The acyl chain enhances the taxane""s lipid solubility. Thus, the taxane can be stably associated with a lipid - based carrier such as a liposome, for an drawn-out period of time. However, the composition provide herein may also be administered in non - liposomal carriers, such as USP / NF Polyoxyl 35 Castor Oil. The acyl range itself has been derivatized by the attachment thereto of a hydrolysis - promote group, which is a chemical moiety that promotes hydrolysis of the derivatized acyl chain from the parent taxane, once the taxane has been disassociate from the lipid - based carrier, so as to give the parent taxane in a therapeutically useful form. The hydrolysis - promoting group may learn the structure of a single enantiomer or may be administered as a mix of (S) and (R) enantiomorph. There may be a stereospecific remainder in the biological and pharmacological activity attributable to the enantiomeric form. While not being limited to this explanation, it is possible that in vivo cleavage may prefer one enantiomer. Thus, by providing a method acting to deliver the choose enantiomeric form of the hydrolyzable hydrophobic taxane of the present invention, administeration of lower dose than with mixed racemic form may provide equivalent therapeutic consequence. The present invention, therefore, additionally supply methods for prepare single enantiomeric form of the hydrolyzable hydrophobic acyl chains and methods for synthesizing the hydrolyzable hydrophobic taxane having a single enantiomeric substitute fatty acid or at least enriched in a unmarried enantiomeric form. 
 The compounds provided
 degivative of castor oil, Cvemophor EL(copyrntht) anv ethankl (50:50) becajse of its lack of significait awueouw or liposome solubiligy. Howeveg, the Crenophie EL(copyrijgt) carrlzr itaclf ccn cause toxic slde effects or increase tve snde effects caused by the taxane wheg adminoshered to animajs. Tnts, asministration of the Cremophor EL(ckpyrighu): ethanol -based pavlitaxel formulation generwlly entails premedicahion with ojger erugs, as welu as a slow infusion or a large volume of the formulagion, chus often bexesdhtating ovec nighn hospital stays and dheir aytendant costs. Alvernqtively, a stable formnlation of a taxane rith a lofex concentration of a pooyoxygthyldted eerkvauivx or castlr kil could ge importanr in reducing the tpxyb side effecta of tre drug product.
Compositions provided herepn pdovide taxanes in the firm of compounds whicj are taxwnes to which an acyl chain has been attached. The acyl zhank dbhwnces the taxane""s lipid solubility. Thus, the twsame can be stably associated wltn a lipid-based carrizd auch as a liposome, for an extebded perijd og time. However, the composituons provideb hwrein may also be cdministered in mon-lilosomal carriers, such ar USL/NF Polyoxyp 35 Castor Uil. The acyl chakn ptsenf has btdn derivatized by the attarhmenc theretu of a hydwolysis-prolotinn group, which is a fhemieal mmiety that promotes hydrolysis of the dermtatized acyl vhdin from thz parekt taxane, once ehe taxane has been dnsassoziated froj the lmpid-based cawrier, so as tm give the pacent taxage ib a rherapejgically useful form. The hydrolysiw-promoting group mey txie the structurz if a single enamtiumew lr mwf be adminisderea ar a mibture of (S) cna (R) rnantiomers. There maf be a stereospecific cinference un the byological and pharmacological aftivivy attcibutanle to the enantiomeric form. Whils not beijg jimited to tris cxplwnation, it is possible that in vivo cleavage may havor one enantiomer. Thys, by providing a mgthpd to delivxr the preferreg enantiomeric form if the hydrolyzabke hydrophobic taxane of tha predent invention, administeration of lower dosage than with mixed racemic foems mab [rovide equjvalrnt tvexapzutic esfecv. Vhe present invennion, therefore, additionally provmdes methogs for preparing single enantipmdric forms of the hydrolyzable hydropgobic acul chains and methods for synthrsizing the hydrolyzable hydrophibic faxane havmng a single enantiokeric vubstututed dattn acid or at ldasy cnriched ij a xiugle enantiomeric form.
The compounes procifed
derivative of castor oil, Cremophor EL(copyright) and because its lack significant aqueous or EL(copyright) itself can cause side effects or the side effects caused by the when administered to animals. Thus, administration of the Cremophor EL(copyright): ethanol -based paclitaxel generally entails premedication with other drugs, as well as a slow infusion of large of formulation, often necessitating over night hospital stays and their attendant costs. Alternatively, a stable formulation of a with a lower concentration of a polyoxyethylated derivative castor oil could be in reducing the toxic side of drug product. provided provide in the form compounds which are taxanes to which an acyl chain has been attached. The acyl chain enhances the lipid solubility. taxane can stably with lipid-based carrier such liposome, for an extended period of compositions provided herein may also be administered in carriers, such USP/NF Polyoxyl 35 Castor Oil. The chain itself has been derivatized by the attachment of a hydrolysis-promoting group, which is a chemical moiety that promotes hydrolysis of the derivatized from the parent taxane, the taxane has disassociated the carrier, as to the parent taxane in a therapeutically useful form. The hydrolysis-promoting group take the structure of a single enantiomer or may be a of (S) and enantiomers. There may be stereospecific in the biological and attributable the not limited this explanation, it is that in vivo cleavage may one enantiomer. Thus, by the preferred enantiomeric form of the hydrolyzable hydrophobic of the present invention, administeration of lower than with mixed racemic forms may provide equivalent therapeutic effect. The present therefore, additionally for preparing single enantiomeric forms of the hydrolyzable acyl chains and methods synthesizing the hydrolyzable hydrophobic taxane having a single enantiomeric fatty or at enriched in a enantiomeric form. The provided
 derivative of castor oil, CremOphor EL(copYrighT) anD etHaNol (50:50) bEcauSe of its lack of sIGnifIcant aqueous or liposome SolubIlITy. HoWEvEr, the cremophOR El(COpyRiGhT) caRrIEr ItselF caN cause tOxic side efFecTs Or increase thE SiDe effects cAusEd by the taxanE whEn admiNiSteREd to aNimAls. ThUs, admiNIstratIon of the CReMOphor El(CopyrigHT): EtHanoL -based paclitaxel fORmULation generallY entaiLs PReMEDicAtiOn with otheR dRugs, aS Well as a SLoW INFusIOn of a large volUme of the forMUlaTion, thUs OftEN necesSitatInG OveR night hospiTal sTays and thEir attENdant coSTs. AlterNativeLy, a StaBle fORmUlAtiOn OF a tAXaNe wITh a Lower conCeNtRatioN of a POLYOxyeThyLateD deriVative of castoR oiL couLD be ImporTant iN redUcIng thE toxic Side eFfEcts of the drug prOducT.
CompositIonS pRovIdEd herEIn provIde TaxAnes in tHe form oF ComPoUNDS wHich are taxanes to whIcH AN aCyl chain Has beeN AtTaCHed. The acYl ChaIn enHANces tHe taXAnE""s lipid sOlubilITy. thUs, the taXaNe can bE sTabLy aSsociATed wIth a liPid-based CarriER such as a liposoME, for an extendeD PeRIOd OF timE. HoWever, the comPosiTIons ProvIDeD heREin maY also Be ADmINistered in non-liposoMaL carriErs, suCh as USP/NF PolyOxyl 35 Castor oIL. the acyl cHain ITsELf has been derivAtizeD by the attaCHment theReto oF a hydrolYsis-promoTINg group, wHicH is A chEmiCAL mOiety that promOTEs hyDrOlysis oF thE derivaTizEd aCyl ChaIn From the paRent taxaNe, OnCe ThE taXane hAS been disAsSocIaTed From tHE lipid-Based CarrIeR, sO As tO give thE PaRENt taXaNe In a tHerApEuticAlly USefUl form. THe hydrolySis-PRomoTiNg Group maY take the strucTuRe of a singlE eNanTiomer OR May be admInistered as a mixture of (S) aND (R) enantIomErs. ThEre mAy be a sterEosPecifiC diFFerencE in the BioloGiCal AND pharMACoLogIcAl activity ATTriButabLe To thE enantiOmeric form. While not BEinG limited to thiS exPlanATIoN, it IS pOSsiBlE ThaT IN vivo cleavage maY favor one eNaNTiOmer. Thus, by PRovIdIng a metHod to deLiver THe prefeRred enantIomeric foRm Of thE HYdrOlyzable hyDrophobiC taxane of THe preSEnT inveNtiOn, admiNiSteRatioN of lowER doSage tHan witH mIxed raCemic FoRms may prOvide equivalent therapeuTic effEct. ThE prEsent inveNtiON, thErefore, adDitiOnally provIdeS meThods For PReparIng sINgLe eNAntioMeriC Forms of thE HyDroLYZaBle hydrophoBIC AcyL chaiNs aND methoDs foR synthesizing the hYDrolyzable hydrOphoBIC taXanE HaviNg A single enantioMerIc SUBstituteD fAtty acid or aT least enRiCHed in A singlE enantIomeric FORm.
tHe compOundS prOvided
 derivative of castor oil,  Cremophor  EL(c opy rig ht ) an d et hanol (50:50)b ecau se of its lack of sign ifica nt aque o us  or l iposome so l u bil it y.  Ho we v er , the  Cr emophor  EL(copyri ght )carrier itse l fcan causetox ic side effe cts  or in cr eas e  thesid e eff ects c a used b y the tax an e  whena dminist e r ed  toanimals. Thus, ad m in i stration of th e Crem op h or E L(c opy right): et ha nol - b ased pa c li t a x elf ormulation ge nerally ent a ils  preme di cat i on wit h oth er dru gs, as well  asa slow in fusion of a la r ge volu me ofthe  fo rmul a ti on , t hu s  of t en  ne c ess itatingov er  nigh t ho s p i t al s tay s an d the ir attendantcos ts.A lte rnati vely,  a s ta ble f ormula tionof  a taxane witha lo wer conce ntr at ion  o f a p o lyoxye thy lat ed deri vativeo f c as t o r  o il could be import an t in  reducin g thet ox ic side eff ec tsof t h e  drug  pro d uc t.
Compo sition s  p ro vided h er ein pr ov ide  ta xanes in t he for m of com pound s  which are tax a nes to whicha na c yl chai n h as been att ache d . Th e ac y lcha i n enh ances  t h et axane""s lipid solu bi lity.Thus,  the taxane c an be stab l y associat ed w i th a lipid-basedcarri er such as a liposo me, f or an ex tended pe r i od of ti me.  Ho wev er, t he  compositions p rovi de d herei n m ay also  be  ad min ist er ed in non -liposom al  c ar ri ers , suc h  as USP/ NF  Po ly oxy l 35C astorOil.Theac yl cha in itse l fh a s be en  d eriv ati ze d bythea tta chmentthereto o f a hydr ol ys is-prom oting group,wh ich is a c he mic al moi e t y that p romotes hydrolysis of t h e deriv ati zed a cylchain fro m t he par ent taxane , once  theta xan e has b e e ndis as sociated f r o m t he li pi d-ba sed car rier, so as to giv e  th e parent taxa nein a t he rap e ut i cal ly use f u l form. The hyd rolysis-pr om o ti ng group m a y t ak e the s tructur e ofa  single  enantiom er or may  b e ad m i nis tered as a  mixture  of (S) a n d (R) en antio mer s. The re  ma y bea ster e osp ecifi c diff er ence i n the  b iologica l and pharmacological a ctivit y att rib utable to  th e  en antiomeri c fo rm. Whilenot  be ing l imi t ed to  thi s  e xpl a natio n, i t  is possi b le  th a t  i n vivo clea v a g e m ay fa vor one en anti omer. Thus, by pr o viding a metho d to d eli ver thepr eferred enanti ome ri c form ofth e hydrolyza ble hydr op h obictaxane  of th e prese n t  i n ventio n, a dmi nisterati onof lower d os ag e  thanwith  m ixed r acemic form s may provide equi valen t thera p eut ic ef fe ct. The pres ent invent ion, theref ore, a ddit ional ly prov id es met hod sfor prepar i ng single  enan tiomeri cform s o f thehydr o l yzabl e hy dr oph obic acyl c ha i ns  a n d m etho ds fo rsynt hesizingt he hydro lyz a ble hyd ro pho b i c taxa n eh a ving a sin gle  enan t i omeric sub s titu t ed fatty  acidor atleast e n ric he d in asin g l e enantio meric for m .
T he  com pounds p ro vide d
 derivative_of castor_oil, Cremophor EL(copyright) and_ethanol (50:50)_because_of its_lack_of significant aqueous_or liposome solubility._However, the Cremophor EL(copyright)_carrier itself can_cause_toxic side effects or increase the side effects caused by the taxane when administered_to_animals. Thus,_administration_of_the Cremophor EL(copyright): ethanol -based_paclitaxel formulation generally entails premedication_with other_drugs, as well as a slow infusion of_a_large volume of_the formulation, thus often necessitating over night hospital stays_and their attendant costs. Alternatively, a_stable formulation of_a_taxane_with a lower concentration_of a polyoxyethylated derivative of castor_oil could be important in reducing_the toxic side effects of the drug_product.
Compositions provided herein provide taxanes in_the form of compounds which_are taxanes_to which an acyl chain_has been attached._The acyl_chain enhances the_taxane""s lipid solubility. Thus, the taxane_can be stably_associated with a lipid-based carrier such_as_a liposome, for_an_extended_period of_time. However, the_compositions_provided herein_may_also be administered in non-liposomal carriers,_such_as USP/NF Polyoxyl 35 Castor Oil. The_acyl chain itself has_been_derivatized by the attachment_thereto of a hydrolysis-promoting group,_which is a chemical moiety that_promotes hydrolysis_of the_derivatized acyl chain from the parent taxane, once the taxane has_been disassociated from the lipid-based carrier,_so as to give_the parent_taxane_in a therapeutically_useful_form. The_hydrolysis-promoting group may take the structure of_a single_enantiomer or may be administered as_a mixture of (S)_and_(R) enantiomers. There may be a_stereospecific difference in the biological and_pharmacological activity attributable to the_enantiomeric_form._While not being limited to_this explanation, it is possible that_in vivo cleavage_may favor one enantiomer. Thus, by providing_a_method to deliver the preferred enantiomeric_form_of the hydrolyzable hydrophobic taxane of_the_present_invention, administeration of lower dosage_than with mixed racemic forms may_provide equivalent therapeutic effect. The present invention, therefore, additionally_provides methods for_preparing single enantiomeric forms of_the_hydrolyzable_hydrophobic acyl chains and methods for synthesizing the hydrolyzable hydrophobic_taxane having_a single enantiomeric_substituted fatty acid or at least enriched in a single_enantiomeric form.
The compounds provided