缩瞳新药(S)-OTS·HCl的制备工艺研究  

Preparation of (S)-OTS·HCl—a new myotic

作　　者：喻轶群[1] 杨丽敏[1] 谢一凡[1] 顾雅芳[1] 顾宙辉 陆阳[1] 

机构地区：[1]上海交通大学医学院药学系,上海200025 [2]上海药谷药业有限公司,上海201203

出　　处：《上海交通大学学报（医学版）》2009年第4期412-415,共4页Journal of Shanghai Jiao tong University:Medical Science

基　　金：上海市教委基金(J50201,06B2009);上海市科委基金(06DZ19001)~~

摘　　要：目的建立以托品醇为原料,通过酰化和拆分制备缩瞳新药(1R,3S,5R,6S)-3α-对甲苯磺酰氧基-6β-乙酰氧基莨菪烷盐酸盐[(S)-OTS.HCl]的工艺。方法运用正交试验优化酰化反应条件并改进拆分工艺;通过高效液相色谱(HPLC)法分析产品光学纯度。结果最佳酰化条件为物料配比n(托品醇)∶n(对甲苯磺酰氯)=1∶1.2,室温下反应5 d;优化的拆分条件为n(外消旋OTS)∶n[L-(-)-二苯甲酰酒石酸]=1∶1.2;(S)-OTS.HCl的总产率为25.6%,光学纯度为98.5%。结论此制备工艺简单、稳定、可控,适合工业化生产。Objective To study the preparation process of hydrochloride of （1R,3S,5R,6S）-3α-paramethyl benzenesulfo- nyloxy-6β-acetoxytropane [ （S）-OTS · HCl] from 6β-acetoxytropine through tosylation and resolution. Methods The conditions of tosylation were optimized by the orthogonal experiment, the resolution process was investigated, and the optical purity of product was determined by high performance liquid chromatogram （ HPLC）. Results The optimal tosylating conditions of 6β-acetoxytropine were： ratio of n （6β-acetoxytropine） to n （p-toluenesulfonyl chloride） was 1：1.2 and the reaction was performed under room temperature for 5 d. The resolution was performed with the ratio of n （ racemic OTS） to n[ （-）-dibenzoyl-L-tartaric acid] 1：1.2. （S）-OTS · HCl was obtained with the yield 25.6% and the optical purity 98.5%. Conclusion The preparation process of （S）-OTS · HCl introduced here is simple, convenient and suitable for scale operation.

关 键 词：托品醇 正交试验 酰化 拆分 (1R  3S  5R  6S)-3α-对甲苯磺酰氧基-6β-乙酰氧基莨菪烷盐酸盐 

分 类 号：TQ463[化学工程—制药化工]