群多普利的合成研究

Study on Synthesis of Trandolapril

目的研究群多普利的合成工艺。方法以1,1,3,3-四甲氧基丙烷为起始原料经部分水解、缩合、脱水、Diels-Alder反应、高压氢化、环合、水解、酯化、硅胶柱手性拆分及催化氢化制得群多普利。结果重要中间体的结构经MS及1H-NMR确证,群多普利的结构经MS、IR、NMR及元素分析确证。结论本法各步反应简单易控,产率高于文献,无需使用昂贵试剂,有工业化潜力。

OBJECTIVE To study the synthesis of trandolapfil. METHODS Trandolapril was synthesized from 1,1,3,3-tetra-methoxypropane by fractional hydrolysation, condensation, dehydration, Diels-Alder reaction, high pressure hydrogenation, cyclizatio-hydrolysation, esterification, chiral resolution on silica gel column and hydrogenation with catalyst. RESULTS Structures of key inter- mediates were confirmed by MS and ^1H-NMR data. The structure of trandolapril was identified by MS, IR, NMR and elemental analysis. CONCLUSION Each step in this route was easily operated and the yield was higher than that reported. This method was successful without using expensive reagents and had the potential for industry.