曲司氯铵的合成工艺研究  

Study on synthetic process of trospium chloride

作　　者：宋伟国[1,2] 杨大伟 高东圣 夏艳 陈禹[1] 方浩[1] 

机构地区：[1]山东大学药学院药物化学研究所,山东济南250012 [2]寿光富康制药有限公司,山东寿光262700

出　　处：《中国药物化学杂志》2016年第5期394-396,共3页Chinese Journal of Medicinal Chemistry

基　　金：山东省自然科学基金杰出青年基金项目(JQ201319;2013-2016)

摘　　要：目的确定并优化曲司氯铵的合成工艺。方法以α-去甲托品醇(2)为原料,经与氯甲酸乙酯发生甲酰化反应制得N-乙氧羰基托品醇(3),3在二环己基碳二亚胺和4-二甲氨基吡啶的作用下与二苯羟乙酸发生酯化反应得到N-乙氧羰基二苯羟乙酸托品酯(4),4经甲酸铵/钯-炭催化氢转移还原体系去除乙氧羰基得到二苯羟乙酸去甲托品酯(5),5与1,4-二氯丁烷缩合成环即得目标物曲司氯铵。结果目标物的化学结构经1H-NM R谱确证且纯度达到99.5%(HPLC法)。结论该法操作简便,总收率为52%(以α-去甲托品醇计),适合工业化生产。Trospium chloride,an antimuscarinic drug,is used for the treatment of overactive bladder disturbances. However,the yield of trospium chloride is too lowto use in industry according to the reported process. To solve this problem,a newmethod was developed starting from α-nortropine,followed by formylation,esterification,catalytic hydrogenation and cyclization. The target compound was identified with the purity over 99. 5%（ HPLC）. The method introduced here was convenient to operate and has a higher yield（ 52%）.

关 键 词：曲司氯铵 尿失禁 M-受体拮抗剂 催化转移氢化 化学合成 

分 类 号：R914.5[医药卫生—药物化学]