新型抗癫痫药盐酸噻加宾的合成  

Synthesis of the antiepileptic tiagabine hydrochloride

作　　者：赵学清[1] 刘秀兰[1] 

机构地区：[1]福建省微生物研究所,福州350007

出　　处：《中国新药杂志》2005年第10期1184-1187,共4页Chinese Journal of New Drugs

基　　金：福建省青年科技人才创新基金(2004J078)

摘　　要：目的:合成GABA摄取抑制剂盐酸噻加宾。方法:以2-溴-3-甲基噻吩和γ-丁内酯为起始原料,经格氏加成,选择性脱水和甲磺酰化成酯,再与(R)-3-哌啶甲酸乙酯进行烃化反应,最后经碱水解和酸化得盐酸噻加宾。结果:未知中间体和目标化合物的化学结构都经结构确证,反应总收率达51.7%(以γ-丁内酯计)。结论:此工艺易于工业化,所用的原料价廉。Objective： To synthesize tiagabine hydrochloride, a GABA uptake inhibitor. Methods： Starting from 2-bromo-3-methyhhiephene and γ-lactone, tiagabine hydrochloride was synthesized via Grignard addition, selective dehydration, sulfonylation, and subsequent N-alkylation of the （3R）-nipecotate, hydrolysis and acidification. Results： The structures of the intermediates and the target compound were confirmed by variety of spectroscopic techniques. The total yield of tiagabine hydrochloride was 51.7 % （based on γ-lactone）. Conclusion： A cost-saving and easily manipulated synthetic route for tiagabine hydrochloride was achieved.

关 键 词：噻加宾 合成 GABA摄取抑制剂 抗癫痫药 

分 类 号：R971.6[医药卫生—药品] R914.5[医药卫生—药学]