脱氟阿托伐他汀钙的全合成  

Total synthesis of desfluoro atorvastatin calcium

作　　者：薛雨[1] 罗刚[1] 王瑛瑛[1] 窦瑶[1] 徐寅正[1] 陈宇瑛[1] 

机构地区：[1]中国医药集团总公司四川抗菌素工业研究所,成都610052

出　　处：《中国新药杂志》2011年第15期1459-1462,共4页Chinese Journal of New Drugs

基　　金：国家科技支撑计划项目(2008BAI55B01)

摘　　要：目的:全合成得到脱氟阿托伐他汀钙,为阿托伐他汀产品质量分析及控制提供重要依据。方法:以异丁酰乙酸乙酯为起始原料,通过胺解,缩合,M ichael-Stetter反应,Paal-Knorr反应,得到关键中间体化合物7,再经酸性条件脱保护及碱性条件酯水解成钠盐,最后与醋酸钙成钙盐得到目标化合物脱氟阿托伐他汀钙。结果:目标化合物结构经1H-NMR、ESI-MS确证。结论:通过该法全合成得到了脱氟阿托伐他汀钙,对阿托伐他汀质量指标的控制具有重要参考价值。Objective： To totally synthesize desfluoro atorvastatin calcium, and to provide important evi- dence for the quality analysis and control of atorvastatin. Methods ： The compound of desfluoro atorvastatin calcium was synthesized by amination, condensation, Michael-Stetter, Paal-Knorrreaction reaction, deprotection from 4- methyl-3-oxo-pentanoic acid ethyl ester. Results： The structures were confirmed by^1 H-NMR and ESI-MS. Conclusion： The target compounds were obtained by this method, which provides an important reference for establishing the quality control indicators of atorvastatin.

关 键 词：脱氟阿托伐他汀 Michael-Stetter反应 Paal-Knorr反应 合成 

分 类 号：R972[医药卫生—药品]