碳青霉烯类抗生素中间体MAP的合成工艺改进  

Improved synthesis of MAP intermediate of carbapenem antibiotics

作　　者：宋明伟 杜伟宏[1] 罗红兵[1] 李颖 丁小东[2] 董宏波[1] 曹胜华[1] SONG Ming-wei;DU Wei-hong;LUO Hong-bing;LI Ying;DING Xiao-dong;DONG Hong-bo;CAO Sheng-hua(Sichuan Industrial Institute of Antibiotics,Research and Reevaluation Key Laboratory of Sichuan Province,Chengdu University,Chengdu 610106,China;Analytical and Testing Center,Sichuan University,Chengdu 610064,China)

机构地区：[1]成都大学,药学院抗生素研究与再评价四川省重点实验室,四川成都610106 [2]四川大学分析测试中心,四川成都610064

出　　处：《化学研究与应用》2021年第11期2269-2275,共7页Chemical Research and Application

摘　　要：本研究报道了一种以4-乙酰氧基氮杂环丁酮(4-AA)为起始原料经过Reformatsky、酰化、还原、亲核取代、Dieckmann环合、烯醇化六步反应得医药中间体β-甲基乙烯基磷酸酯(MAP)的方法,通过单因素对照实验对关键反应的重要参数进行了优化,得到一条收率高、成本低和高效的合成路线,总收率达到43%,液相纯度达到98.82%,并采用MS和^(1)HNMR对关键中间体和产物都进行了表征。β-Methyl vinyl phosphate(MAP),the intermediate of 1-β-carbapenem antibiotics were prepared from 4-acetoxyazetidin-2-one(4-AA)via Reformatsky,acylation,reduction,nucleophilic substitution,Dieckmann cyclization,and enolization.The important parameters of the key reaction were optimized through single-factor control experiments,and a synthetic route with high yield,low-cost and high efficiency was obtained,the total yield reached 43%,and the liquid phase purity reached 98.82%.The structures of the product were characterized by MS and ^(1)HNMR.

关 键 词：碳青霉烯类抗生素 MAP 中间体 

分 类 号：O621.3[理学—有机化学]