Naxaprostene, CG-4305
那前列烯 11-(环戊-2-烯基)十一烷酸 Chemical Name: [2E,3aalpha,4alpha(1E,3R*),5beta,6aalpha]-3-[[4-(3-Cyclohexyl-3-hydroxy-1-propenyl)hexahydro-5-hydroxy-2(1H)-pentalenylidene]methyl]benzoic acid; [2E,3aS*,4R*(1E,3S*),5R*,6aS*]-3-[[4-(3-Cyclohexyl-3-hydroxy-1-propenyl)hexahydro-5-hydroxy-2(1H)-pentalenyliden]methyl]benzoic acid; (5E)-2,3,4-Trinor-1,5-inter-m-phenylene-6a-carba-16,17,18,19,20-pentanor-15-cyclohexylprostacyclin
CAS No. 87269-59-8, 89955-40-8 (racemate)
项目整合开发状态: Phase II
项目研究机构: Gr黱enthal (Originator)
合成路线:Monoketal (I) is acylated with dimethylcarbonate to (II),reduced with NaBH4 to give (III) and protected with tert-butyldimethylsilylchloride to give (IV).After selective reduction of the ester function of (IV) with DIBAH,the resulting aldehyde (V) undergoes a Wittig-Horner-reaction with dimethyl 2-oxo-2-cyclohexylethylphosphonate to give (VI),which is subsequently reduced with NaBH4.After separation of the epimeric alcohols by silica flash chromatography,(VII) is deprotected with a AcOH/THF/water mixture.Wittig reaction of 3-methoxycarbonylphenylmethylene-triphenylphosphorane with (VIII) gives a mixture of E/Z-isomers,which is separated by preparative HPLC.Ester hydrolysis with KOH and acidification of the E-isomer gives naxaprostene (IX),R = H.
📌 参考资料/链接：
参考文献标题:New cis-bicyclo[3.3.0]octane derivs.,medicines containing them and processes for the preparation of these compds.and medicines
文献作者:B鰄lke,H.; Loschen,G.; Michel,G.; M黮ler,B.(Gr黱enthal GmbH)
参考来源:DE 3146278
📄 详细内容
合成路线:Monoketal (I) is acylated with dimethylcarbonate to (II),reduced with NaBH4 to give (III) and protected with tert-butyldimethylsilylchloride to give (IV).After selective reduction of the ester function of (IV) with DIBAH,the resulting aldehyde (V) undergoes a Wittig-Horner-reaction with dimethyl 2-oxo-2-cyclohexylethylphosphonate to give (VI),which is subsequently reduced with NaBH4.After separation of the epimeric alcohols by silica flash chromatography,(VII) is deprotected with a AcOH/THF/water mixture.Wittig reaction of 3-methoxycarbonylphenylmethylene-triphenylphosphorane with (VIII) gives a mixture of E/Z-isomers,which is separated by preparative HPLC.Ester hydrolysis with KOH and acidification of the E-isomer gives naxaprostene (IX),R = H.
参考文献标题:Designing prostacylin analogues
文献作者:Floh? L.; B鰄lke,H.; Frankus,E.; et al.
参考来源:Arzneim-Forsch Drug Res 1983,33(9),1240-8
合成路线:Monoketal (I) is acylated with dimethylcarbonate to (II),reduced with NaBH4 to give (III) and protected with tert-butyldimethylsilylchloride to give (IV).After selective reduction of the ester function of (IV) with DIBAH,the resulting aldehyde (V) undergoes a Wittig-Horner-reaction with dimethyl 2-oxo-2-cyclohexylethylphosphonate to give (VI),which is subsequently reduced with NaBH4.After separation of the epimeric alcohols by silica flash chromatography,(VII) is deprotected with a AcOH/THF/water mixture.Wittig reaction of 3-methoxycarbonylphenylmethylene-triphenylphosphorane with (VIII) gives a mixture of E/Z-isomers,which is separated by preparative HPLC.Ester hydrolysis with KOH and acidification of the E-isomer gives naxaprostene (IX),R = H.
参考文献标题:NAXAPROSTENE
文献作者:Winter,W.
参考来源:Drugs Fut 1990,15(3),233
合成路线:Monoketal (I) is acylated with dimethylcarbonate to (II),reduced with NaBH4 to give (III) and protected with tert-butyldimethylsilylchloride to give (IV).After selective reduction of the ester function of (IV) with DIBAH,the resulting aldehyde (V) undergoes a Wittig-Horner-reaction with dimethyl 2-oxo-2-cyclohexylethylphosphonate to give (VI),which is subsequently reduced with NaBH4.After separation of the epimeric alcohols by silica flash chromatography,(VII) is deprotected with a AcOH/THF/water mixture.Wittig reaction of 3-methoxycarbonylphenylmethylene-triphenylphosphorane with (VIII) gives a mixture of E/Z-isomers,which is separated by preparative HPLC.Ester hydrolysis with KOH and acidification of the E-isomer gives naxaprostene (IX),R = H.
参考文献标题:The crystal structure of CG 4305,a biologically active prostacyclin analogue with exceptional chemical and metabolic stability
文献作者:Stezowski,J.J.; Floh? L.; B鰄lke,H.
参考来源:J Chem Soc Chem Commun 1983,1315-6
产品链接: CAS No. 87269-59-8›› 产品链接: CAS No.89955-40-8››