gcle的合成工艺研究.pdf

南昌大学硕士学位论文 GCLE的合成工艺研究姓名:栾伟丽申请学位级别:硕士专业:化学工程指导教师:肖鉴谋 20071201 摘要摘要随着发酵技术的发展,己大幅度降低了青霉素的生产成本,根据青霉素与头孢菌素分子结构的相似性,。 GCLE()(7-ACA)(7-ADCA)之后合成头孢菌素药物又一新的重要中间体,以GCLE为原料可方便地制得各类头孢菌素衍生物。,以及GCLE本身的工艺技术水平不断提高,GCLE也将会有更广阔的市场。本文介绍GCLE 的用途、研究现状、合成工艺及应用前景;重点研究以青霉素为原料通过氧化、酯化、扩环、还原,卤化等步骤合成GCLE的工艺。本研究采用的合成路线为:以青霉素G钾盐为原料,选用工业过氧化氢制备的过氧乙酸(%)%为氧化剂,氧化得青霉素亚砜;采用对硝基溴苄为酯化试剂,制备青霉素亚砜酯;以NCP(N-氯代邻苯二甲酰亚胺)为开环试剂,酞酰亚胺钾和4A型分子筛为酸清除剂,顺利开环;再经无水SnCh ,最终产率在60%以上。此合成路线可提高产率,具有反应条件温和,操作简便安全,更接近工业化生产要求等特点, 各步反应产物经过红外光谱、核磁共振、物理分析等方法证实与目标产物一致。同时尝试了其他合成方法,用Morin转换来获得扩环产物,发现重现性差, 不利于工业化生产。并尝试对扩环产物进行还原,以甲苯为溶剂,PCh为氯化试剂,三乙胺为有机碱,改变有机碱和溶剂,,但结果不理想有待于进行进一步的探索。关键词:GCLE,氧化,酯化,扩环,还原 Abstract ABSTRACT Withthedevelopment offermentationtechnique,the costofpenicillin has been reduced more,based on thesimilarofpenicillin and cephalosporin,it e the subject thatpeople concern generally frompenicillin tocephalosporin witllchemical conversion. GCLE isanother new andimportant intermediate tosynthesize medication of cephalosporin besides 7-ACA and7- can synthesize allmanner of cephalosporin derivatives the increase ofproduct mixofdomestic 13-1actamase modified 3-location antibiotic,as wellastheimprovement ofGCLE’S production process,GCLE willhave large application ofGCLE,the studystatus,thesynthesize technology and theprospect were introduced inthispaper. We use thepenicillin as starting material through oxidation,esterification,ring enlargement,deoxidation and halogenation and SO on. The synthetic route starts from penicillin G peroxyaceticacid(%)as Oxidizing Agent togetpenicillin G sulfoxide;esterifided withp-nitrobenzyl bromine tosynthesize penicillin G sulfoxide ester;we synthesize3-exomethylenecepham sulfoxide ester withphthalimidepotassium and 4Amolecular sieveas acidscavenger toopen thering,SnCh ascatalyzation toclose