碳青霉烯骨架的合成研究

Synthesis of carbapenem skeleton

目的研究一条适合工业化生产的碳青霉烯母环骨架(1)新合成路线。方法以(3S,4R)-4-乙酰氧基-3-[(1R)-(叔丁基二甲硅氧基)乙基]氮杂环丁烷-2-酮(简称4-AA)为起始原料,与自制的一种手性辅助剂在锌粉催化下,经Reformatsky反应、水解、引入β-羰基酯结构、脱保护、环合,经氯磷酸二苯酯活化得1。优化关键工艺的参数,经MS、GC-MS和1H NMR确证中间体及目标化合物。结果与结论合成总收率达19.9%。该路线经工艺改进后反应条件温和,操作简便,适合工业化生产。

Objective To investigete a new synthetic route for carbapenem skeleton（1）for industrial production. Methods（3 S,4 R）-4-acetoxy-3-[（1 R）-（tert-butyldimethylsilyloxy）ethyl]azetidin-2-one（4-AA）was used as raw material,and 1 was obtained from it through a homemade chiral auxiliary zinc powder catalyzed Reformatsky reaction,hydrolysis,the introduction of β-carboxyl ester structure,deprotection,cyclization,and activation by diphenyl chlorophosphate. The each key process was optimized,and the structures of intermediate and target compounds were confirmed by MS,GC-MS and1 H NMR. Results and Conclusion The total yield was 19.9%. The improved process conditions are mild,easy to operate,and suitable for industrial production.