帕尼培南关键中间体的合成

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

目的改进帕尼培南关键中间体(S)-1-[N-(对硝基苄氧羰基)-1-亚胺基乙基]-3-巯基吡咯烷的合成工艺。方法以对硝基苄醇为起始原料,经酰化、缩合、与3-R-羟基吡咯烷发生N-烃基化反应,再经磺酰化、缩合、水解反应得到目标化合物。结果与结论以对硝基苄醇为起始原料经6步反应得到目标化合物,结构经IR、1H-NMR、MS谱图数据确证,比旋光度值与文献报道一致。改进后的工艺总收率为37.2%,各步反应操作简便,条件温和,更适合工业化生产。

Aim To synthesize panipenem intermediate,（S）-1-[N-（p-nitrobenzyloxycarbonyl）-acetimidoyl]-3-mercaptopyrrolidine.Methods The target compound was obtained from 4-nitrobenzy1 alcohol as starting material by acylation,condensation,reaction with 3R-hydroxyl-pyrrolidine,then sulfonylation,condenation and hydrolysis.Results and conclusion The structure of target compound was confirmed by the spectra of IR,1H-NMR,MS.Compared with the synthetic process reported in the literature,this optimal synthetic procedure is simple and suitable for industrialized production with lower cost and higher yield;the overall yield is 37.2% based on p-nitrobenzyl alcoho1.