头孢菌素类药物中间体GCLE的合成研究进展

综述了头孢菌素类药物中间体7-苯乙酰胺-3-氯甲基头孢烷烯酸对甲氧基苄酯的合成工艺。其合成路线主要有闭环前卤化法和闭环后卤化法两种,其中闭环前卤化法是先将青霉素亚砜酯开环后与捕捉剂作用,然后再进行烯丙位的氯化,最后闭环,该法应用广泛,但氯化采用电解饱和食盐水,条件不易控制;闭环后卤化法可分为3-环外亚甲基头孢烷酸直接卤化法、7-ADCA光溴化法、3位的-CH2OH直接卤化,该法研究较早,但成本偏高。

Research progress in the synthesis of cephalosporin intermediate GCLE

This paper summarizes the synthetic routes and purification methods about 7-phenylacetamide-3-chloromethyl-3-cepham-4-carboxylic acid p-methyl-oxybenzyl ester(GCLE) of cephalosporin intermediate.The synthesis routes of GCLE mainly included pre-ring closure reaction halogenation and post-ring closure reaction halogenation.Pre-ring closure reaction halogenation is that using trapping agent to capture the penicillin sulfoxide ester,and then chlorinating at the allyl position,producing the GCLE by the ring closure reaction.However,the common methods of the post-ring closure reaction halogenation have three types,the direct chlorination of cephalothin,the photo-bromination of 7-ADCA as crude material and the direct halogenation of hydroxyl methyl at 3 position of-CH2OH.By the above literature investigation,each process route was compared.