利福平合成工艺研究  

Study on synthesis of rifampicin

作　　者：丁毓 吴艳阳[1] 张相洋[2] 朱家文 陈葵[1] 武斌[1] 纪利俊[1] DING Yu;WU Yan-yang;ZHANG Xiang-yang;ZHU Jia-wen;CHEN Kui;WU Bin;JI Li-jun(Chemical Engineering Research Center,East China University of Science ＆ Technology,Shanghai 200237,China;State Key Laboratory of Chemical Engineering,East China University of Science ＆ Technology,Shanghai 200237,China)

机构地区：[1]华东理工大学化学工程研究所,上海200237 [2]华东理工大学化学工程国家重点实验室,上海200237

出　　处：《现代化工》2018年第10期123-126,128,共5页Modern Chemical Industry

基　　金：上海浦江人才计划项目(16PJD019);国家自然科学基金(21406071)

摘　　要：为了提高利福平的产品质量,对目前国内普遍使用的嗪工艺进行了研究与优化。直接以发酵液氧化萃取制得的利福霉素S为原料进行环合反应和缩合反应合成利福平,与以往的利福霉素S钠盐为原料相比,无需利福霉素S钠盐的结晶、分离、干燥及酸化过程,生产工艺更为简单。考察了环合反应温度和时间、缩合反应温度和时间、原料配比及相关的催化剂用量对利福平收率和纯度的影响。得到较优工艺条件为:环合反应温度为55℃,环合反应时间为1.5 h,V(N,N-二羟甲基叔丁胺)∶V(冰醋酸)∶m(抗坏血酸)∶m(利福霉素S)=0.278∶0.014∶0.014∶1.000,缩合反应温度为55℃,缩合反应时间为2 h,V(1-甲基-4-氨基哌嗪)∶m(利福霉素S)=0.463∶1.000,此时,利福平粗品的收率可达86.56%,纯度为92.69%。Rifampicin is an important drug against tuberculosis,with large market demand.To improve the quality of rifampicin,the rifampicin synthesis process via oxazine,which is widely used in China,is studied and optimized.Rifampicin can be synthesized through cyclization and condensation reactions of rifamycin S that is prepared directly by oxidation and extraction of zymotic fluid,which is simpler without the crystallization,separation,drying and acidification for rifamycin S sodium salt compared with the traditional process that uses rifamycin S sodium salt as raw material.The effects of temperature and time of cyclization,temperature and time of condensation,ratios among raw materials and dosage of catalyst on the yield rate and purity of rifampicin product are investigated.The appropriate conditions obtained are listed as follows：55℃ and 1.5 h for the cyclization reaction,V（N,N-dihydroxymethyl tertbutylamine） ∶ V（glacial acetic acid） ∶ m（ascorbate acid） ∶ m（rifamycin S） = 0.278∶0.014∶0.014∶1.000,55℃ and 2 h for the condensation reaction,V（1-methy-4-aminopiperazine）∶m（rifamycin S） = 0.463∶1.000.Under these conditions,the yield rate and purity of crude rifampicin product can reach 86.56% and 92.69%,respectively.

关 键 词：利福霉素S 环合反应 缩合反应 利福平 收率 

分 类 号：TQ465.5[化学工程—制药化工]