(2S,4S)-1-烯丙氧羰基-2-(氨磺酰氨基)甲基-4-巯基吡咯烷的合成

Synthesis of(2S,4S)-1-allyl-4-mercapto-2-((sulfamoylamino)-methyl)pyrrolidine-1-carboxylate

目的烯丙氧羰基保护的多利培南侧链的合成。方法以反式-4-羟基-L-脯氨酸为起始原料,经酯化、N-酰化、甲烷磺酰化、还原、SN2取代反应、Mitsunobu缩合反应、水解7步合成了多利培南关键中间体(2S,4S)-1-烯丙氧羰基-2-(氨磺酰氨基)甲基-4-巯基吡咯烷(1),总收率为32.5%。结果目标化合物和关键中间体经1H-NMR、MS谱确证。结论各步反应操作简便,条件温和,有利于工业化生产。

Objective Synthesis of an important side chain of the novel carbapenem antibiotic doripenem. Methods The side chain of doripenem was synthesized with trans-4-hydroxy-L-proline as a starting material in 7 steps including esterification, N-acylation, methanesulfonyl, reduction reaction, SN2 substitution reaction, Mitsunobu condensation reaction and hydrolysis reaction. The total yield was 32.5%. Results Target compounds and key intermediates were evidenced by 1H-NMR and MS spectrum. Conclusion The reactions are easy to operate under mild conditions, and can be conducive to industrial production.