盐酸头孢吡肟的合成  

Synthesis of cefepime hydrochloride

作　　者：彭东明[1,2] 王晓红[1] 刘艳飞[1] 尹伟成 刘珍宝[3] 张航[1] 张姗姗[1] 

机构地区：[1]中南大学化学化工学院,湖南长沙410083 [2]湖南中医药大学药学院,湖南长沙410208 [3]中南大学药学院,湖南长沙410013

出　　处：《中南大学学报（自然科学版）》2015年第7期2405-2411,共7页Journal of Central South University:Science and Technology

基　　金：国家自然科学基金资助项目(81301258);湖南省科技计划项目(2012SK3134);湖南省自然科学基金资助项目(13JJ3099)~~

摘　　要：以7-氨基头孢烷酸(7-ACA)为原料,二氯甲烷和环己烷为溶剂,三甲基氯硅烷(TMSCl)为保护剂,与N-甲基吡咯烷(NMP)和三甲基碘硅烷(TMSI)制成的季铵盐中间体反应,脱保护后成盐得中间体7-氨基-3-(1-甲基-1-四氢吡咯)甲基-3-头孢-4-羧酸盐酸盐(7-MPCA),再与苯并噻唑硫醇活性酯反应,合成目标产物盐酸头孢吡肟。研究硅烷化反应、碘代反应和成盐反应的主要影响因素,进行工艺参数优化。采用红外光谱、元素分析、核磁共振谱和质谱对产物盐酸头孢吡肟进行结构表征。研究结果表明:该工艺原材料易得,反应条件温和,且操作简单,以7-ACA的质量计盐酸头孢吡肟的总收率为74.6%。The intermediate 7-MPCA was obtained by being salified after deprotection based on the reaction of the intermediate of quaternary ammonium salt produced by N-methyl pyrrolidine （NMP） and trimethyliodosilane （TMSI）, and 7-aminocephalosporanic acid （7-ACA） was used as raw material, dichloromethane and cyclohexane as solvents, and trimethylchlorosilane （TMSC1） as the protective agent. Cefepime hydrochloride was synthesized from 7-amino-3-[（1-methyl-l-pyrrolidino） methyl]-3-cephem-4-carboxylic acid （7-MPCA） with benzothiazolethiol active ester. The main influencing factors of reactions such as silylation, iodization and salification were analyzed, and the process parameters were optimized. The structure of cefepime hydrochloride was confirmed by IR, elemental analysis, NMR and MS. The results show that the improved synthetic method has some advantages, such as easy availability of raw materials, mild reaction condition, and simple operation. The total yield of cefepime hydrochloride is 74.6% based on the mass fraction of 7-ACA.

关 键 词：7-氨基头孢烷酸 盐酸头孢吡肟 药物合成 抗生素 

分 类 号：R914.5[医药卫生—药物化学]