左旋盐酸去甲基苯环壬酯的合成新方法  

Facile synthetic method of levodesmethylphencynonate hydrochloride

作　　者：何新华[1] 张凭[1] 阎远[1] 仲伯华[1] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850

出　　处：《中国药物化学杂志》2011年第5期379-382,共4页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金项目(30973615);"重大新药创制"科技重大专项(2009ZX09102-038)

摘　　要：目的合成新型M4受体选择性拮抗剂左旋盐酸去甲基苯环壬酯。方法以苄胺为原料制备N,N-二乙氧基甲基苄胺,该苄胺与环己酮反应、选择性还原,再与(R)-α-苯基-α-环戊基-α-羟基乙酸甲酯反应,经氢化、成盐得到目标产物左旋盐酸去甲基苯环壬酯,总收率为8.0%。结果与结论目标化合物的结构经元素分析、核磁共振氢谱、质谱确证。新方法操作简便,以新旧合成路线中共有贵重原料(R)-α-苯基-α-环戊基-α-羟基乙酸甲酯计算,产品收率较原方法提高了10.6%,降低了成本,且利于环保。Levodesmethylphencynonate hydrochloride（1）,a novel selective M4 muscarine receptor antagonist,has been chosen as a candidate of anti-Parkinson′s disease drug characterized by its good efficiency,high selectivity and low toxicity.A new synthetic method in the search for more economical and environmental friendly process was developed.The starting compound N,N-diethoxylmethy benzyl amine was prepared by benzyl amine and ethanol,then via Mannich reaction with cyclohexanone,afterwards selective hydrogenation and ester exchange with（R）-methyl-α-phenyl-α-cyclopentyl-α-hydroxy acid ester,hydrogenation,saltization to obtain target compound（1）.The overall yield was 8.0%,which increased 10.6% based on common chiral raw material（R）-methyl-α-phenyl-α-cyclopentyl-α-hydroxy acid ester.The chemical structure of levodesmethylphencynonate hydrochloride was characterized by MS,1H-NMR and element analysis.Compared with the original synthetic process,the new route is facile and suitable for industrialized production with lower cost,lower pollution and higher yield.

关 键 词：工艺改进 化学合成 左旋盐酸去甲基苯环壬酯 

分 类 号：R914[医药卫生—药物化学]