阿托伐他汀钙对映异构体(S,S)的全合成

Total Synthesis of (3S,5S)-epimers of Atorvastatin Calcium

合成阿托伐他汀钙对映异构体。方法:以(R)-4-氯-3-羟基丁酸乙酯为起始原料经氰基化、Claisen缩合、羰基还原、O-烃化、氰基还原、与M-4发生Paal-Knorr反应、脱保护、酯水解、成盐等共9步反应合成了阿托伐他汀钙对映异构体(1)。其结构经1H-NMR、ESI-MS、HPLC确证。结论:合成得到了目标化合物,可为阿托伐他汀钙的杂质研究提供可靠参数。

Objective： To synthesis （3S,5S）-epimers of Atorvastatin Calcium. Methods： the （R）-ethyl-4-chloro-3-hydroxybutanoate was used a.s raw material and the （3S,5S）-epimers of Atorvastatin Calcium was obtained by cyanidation, condensation of carbonyl group, O-alkylation,condensation of cyanogroup, Paal-Knorr reaction with M-4, deprotection, hydrolysis of ester, salinization. The structures were confirmed by 1^H-NMR, ESI-MS, HPLC. Conclusion： The target compound was synthesized by this method, which provides an important reference for the research on impurities of atorvastatin.