拉米夫定的合成工艺探讨  

Research on Synthesis Technology of Lamivudine

作　　者：陈朗秋[1] 刘永青[1] 刘开科[1] 史慎德[1] 高清姣[1] 余晓琼[1] 

机构地区：[1]湘潭大学化学学院环境友好化学与应用省部共建教育部重点实验室,湖南湘潭411105

出　　处：《湘潭大学自然科学学报》2010年第4期78-83,共6页Natural Science Journal of Xiangtan University

基　　金：湖南省自然科学基金项目(05JJ40054);第二批湖南省大学生研究型学习与创新实验计划项目(批准号:No.87)

摘　　要：拉米夫定是具有抗HIV和抗HBV生物活性的2′-脱氧核苷酸类似物.以溴代乙酸、乙醛酸为不同的起始原料合成中间体二羟基乙醛酸薄荷酯,比较两种工艺发现:乙醛酸为原料的工艺路线较短,费用较低;二羟基乙醛酸薄荷酯与2,5-二羟基-1,4-二噻烷成环反应、氯化、偶联、还原反应可以合成拉夫米定.同时,改进了合成和分离工艺,总收率达到22.5%.改进后的工艺路线较短,操作简便,适合于工业化生产.Lamivudine is a 2＇-deoxy nucleoside analogue with a biological importance of an anti-HIV and anti-HBV.On the comparison of two technologies that the intermediate menthyl dihydroxy glycoxylate was synthesized with bromoacetic acid or glycoxylic acid as a different raw material,the synthetic technology is discovered shorter steps and lower cost with glycoxylic acid as a raw material.Menthyl dihydroxy glycoxylate was reacted to cyclization with 2,5-dihydroxy-1,4-dithiane,subsequent chlorinated,coupled,and reduced to obtain lamivudine.Meanwhile,the synthesis and separation technology was improved,and the overall yield is reached 22.5%.The improved technology herein is applicable to industrial production as the advantage of shorter steps,concise and practical operation.

关 键 词：拉米夫定 抗病毒药物 合成 

分 类 号：TQ460.6[化学工程—制药化工]