(S)-1-(N-烯丙氧羰基)亚胺乙基-3-巯基吡咯烷的合成

Synthesis of (S)-1-[N-(allyloxycarbonyl)acetimidoyl]-3-mercaptopyrrolidine

目的合成帕尼培南关键中间体(S)-1-(N-烯丙氧羰基)亚胺乙基-3-巯基吡咯烷。方法以氯甲酸烯丙酯为酰化剂,与盐酸乙脒进行N-酰化反应得到1-亚胺乙基氨基甲酸烯丙酯,该化合物与3-R-羟基吡咯烷进行缩合,再经甲磺酰化、SN2取代、水解共5步反应得到目标化合物。该合成路线中使用新型保护基烯丙氧羰基替代传统的保护基——对硝基苄氧羰基。结果与结论目标化合物的结构经1H-NMR、MS谱确证,总收率为41.6%,各步反应操作简便,条件温和,有利于工业化生产。

（S） - 1 - [ N- （ allyloxycarbonyl ） acetimidoyl ] -3-mercaptopyrrolidine （ 1 ） was the key intermediate of panipenem, which was a kind of carbapenem antibiotic. In the traditional method of synthesizing panipenem, the protecting group was removed by catalytic hydrogenation,and the product was purified by macroporous resin. In this synthetic process, allyloxycarbonyl as a new protection group was used instead of p-nitrobenzy- loxycarbonyl to synthesize compound 1. The target compound was synthesized from allyl chloroformate and acetamidine hydrochloride through 5 steps, N-acylation, condensation, sulfonylation, substitution reaction and hydrolysis. The chemical structure was confirmed by MS and 1^H-NMR. The overall yield was 41.6%. This new route was provided with mild condition, easy operation and suitable for industrialized production.