头孢类抗生素母核ACLE合成纯度的条件优化  

Optimization of Synthetic Purity of ACLE in Cephalosporin Antibiotic Mother Nucleus

作　　者：卢荣桂 何小鹏 Lu Ronggui;He Xiaopeng(Zhejiang Dongbang Phannaceutical Co.,Ltd.,Zhejiang,317101)

机构地区：[1]浙江东邦药业有限公司,浙江317101

出　　处：《当代化工研究》2020年第18期161-162,共2页Modern Chemical Research

摘　　要：头孢类抗生素是分子中含有头孢烯的半合成抗生素,头孢类抗生素得到了广泛的应用。ACLE(7-氨基-3-氯甲基-3-头孢环-4-羧酸对甲氧苄酯)是7位侧链开始的合成路线中重要的中间体,是头孢母核,对头孢类药物合成质量和效率有显著的影响。本文以从7位侧链开始的头孢洛扎合成路线中制备工艺条件开展研究优化。对ACLE的同分异构体进行分析,并控制同分异构体的生成条件,优化ACLE的纯度。对反应底物滴加温度、异丁醇反应温度对ACLE-HCl产率的影响进行探究。结果显示3-氯甲基-7-苯基乙酰氨基头孢菌素对甲氧基苄基酯(GCLE)反应温度为0℃条件下,ACLE-HCl同分异构体较少,产物较纯,可以达到99.3%,反应底物异丁醇滴加温度为0℃条件下,获得较高的ACLE-HCl产率,反应温度对ACLE-HCl产率和纯度均有影响。Cephalosporins are semi synthetic antibiotics containing cephalosporins,and cephalosporins have been widely used.ACLE(7-amino-3-chloromethyl-3-cefcyclo-4-carboxylic acid p-methoxybenzyl ester)is an important intermediate in the synthesis of 7-position side chain,and it is the mother nucleus of cephalosporin,which has a significant impact on the synthesis quality and efficiency of cephalosporins.In this paper,the preparation conditions of cefprozac starting from 7-position side chain were studied and optimized.Analyze the isomers of ACLE,control the generation conditions of isomers,and optimize the purity of ACL.The effects of substrate dropping temperature and isobutanol reaction temperature on the yield of ACLE HCl were studied.The results showed that under the condition of GCLE reaction temperature of 0℃,there were fewer isomers of ACLE HCl and the product was pure,which could reach 99.3%.Under the condition of isobutanol dropping temperature of reaction substrate of 0℃,the yield of ACLE HCl was higher.The reaction temperature had an effect on the yield and purity of ACLE HCl.

关 键 词：头孢类抗生素 ACLE GCLE 合成 

分 类 号：TQ[化学工程]