阿托伐他汀钙中间体的合成  

Synthesis of the Intermediate of Atorvastatin Calcium

作　　者：张立光[1] 於学良[1] 吴芝园[1] 丁荣敏[1] 俞学炜[1] 

机构地区：[1]苏州卫生职业技术学院,江苏苏州215009

出　　处：《中国医药工业杂志》2013年第10期975-977,共3页Chinese Journal of Pharmaceuticals

基　　金：苏州市科技发展计划项目(STSD2011072)

摘　　要：(3S)-4-溴-3-羟基丁酸乙酯经缩合、不对称生物催化还原及羟基保护制得[(4R,6S)-6-溴甲基-2,2-二甲基-1,3-二氧杂环己烷-4-基]乙酸叔丁酯(5),5在溴化亚铜及含氮化合物配体作用下与硝基甲烷缩合后,经雷尼镍催化氢化还原制得阿托伐他汀钙中间体[(4R,6R)-6-(2-氨基乙基)-2,2-二甲基-1,3-二氧杂环己烷-4-基]乙酸叔丁酯,总收率约41%。tert-Butyl [ （4R,6R）-6-（2-aminoethyl）-2,2-dimethyl-l,3-dioxan-4-yl] acetate, the intermediate of atorvastatin calcium, was synthesized from （3S）-ethyl-4-bromo-3-hydroxybutanoat by condensation, asymmetric biocatalytic reduction and hydroxyl protection to give tert-butyl E （4R,6S）-6-bromomethyl-2,2-dimethyl-l,3-dioxan-4- yl] acetate, which was subjected to condensation with CH3NO2 in the presence of CuBr/ligand, followed by reduction with an overall yield of about 41%.

关 键 词：[(4R 6R)-6-(2-氨基乙基)-2 2-二甲基-1 3-二氧杂环己烷-4-基]乙酸叔丁酯 阿托伐他汀钙 降血脂药 中间 体 合成 

分 类 号：O623.624.1[理学—有机化学]