抗丙肝病毒药物维帕他韦的六步法合成研究  

Study on the Six-Step Synthesis of the Anti-hepatitis C Virus Drug Vepatasvir

作　　者：张兆佳 徐瑞雪 詹红菊[1] 范伟伟 李立威[1] ZHANG Zhaojia;XU Ruixue;ZHAN Hongju;FAN Weiwei;LI Liwei(College of Chemical Engineering and Pharmacy,Jingchu University of Technology,Jingmen 448000,China;School of Chemical Engineering and Pharmacy,Wuhan Institute of Technology,Wuhan 430000,China)

机构地区：[1]荆楚理工学院化工与制药学院,湖北荆门448000 [2]武汉工程大学化工与制药学院,湖北武汉430000

出　　处：《生物化工》2024年第5期165-168,176,共5页Biological Chemical Engineering

基　　金：湖北省科技重点研发计划(大健康领域支持地方专项)(2022BCE023);湖北省大学生创新创业训练计划项目(S202311336009);荆门市重点科技计划项目(2022YFZD004);荆楚理工学院科研项目(ZX202403)。

摘　　要：以国内已实现批量生产供应的1b和1a为原料,经缩合反应制备化合物1。在碳酸铯的作用下,化合物1和2a发生反应,生成化合物2。随后,化合物2通过与醋酸铵的作用,形成化合物3。化合物3通过氧化脱氢反应,生成重要的化合物4。将叔丁氧羰基从化合物4中脱离出来,可以制备化合物5。化合物5在2-氯-4,6-二甲氧基-1,3,5-均三嗪作用下与MOCD-苯甘氨酸进行酰胺缩合反应,得到目标化合物维帕他韦(化合物6)。本合成方法具有路线短,原辅料便宜易得,各步反应条件温和,操作简单、安全等优点。Compound 1 is prepared by condensation reaction using 1b and 1a,which have already been massproduced and supplied domestically,as raw materials.Under the action of cesium carbonate,compound 1 and 2a react to form compound 2.Subsequently,compound 2 reacted with ammonium acetate to form compound 3.Compound 3 undergoes oxidative dehydrogenation reaction to generate the important compound 4.By separating the tert butoxycarbonyl group from compound 4,compound 5 can be prepared.Compound 5 undergoes amide condensation reaction with MOC-D-phenylglycine under the action of 2-chloro-4,6-dimethoxy-1,3,5-triazine to obtain the target compound vipatavir(Compound 6).This synthesis method has the advantages of short route,cheap and easy to obtain raw materials,mild reaction conditions in each step,simple operation,safety,etc.

关 键 词：维帕他韦 合成 工艺优化 

分 类 号：O621.3[理学—有机化学]