摘要
吉米沙星是一种新型喹诺酮类抗菌剂,其支链是影响其药效的最重要部分,对药理活性有决定性影响。文章综述了吉米沙星支链的合成方法,并对各种方法进行比较分析,总结出各自的优缺点。采用氧化剂法合成吉米沙星支链,反应条件温和,总收率最高可达39.6%,三废污染少。此工艺中的中间体3(4-氰基-1-(N-叔丁氧羰基)吡咯烷-3-酮)还原成中间体4’(4-氨甲基-1-(N-叔丁氧羰基)吡咯烷-3-醇)时,宜采用硼氢化物―氯化盐为还原剂;中间体5’(4-(N-叔丁氧羰基)氨甲基-1-(N-叔丁氧羰基)吡咯烷-3-醇)氧化成中间体6(4-(N-叔丁氧羰基)氨甲基-1-(N-叔丁氧羰基)吡咯烷-3-酮)时,宜采用Jones试剂为氧化剂,收率及纯度高,易于操作。
Gemifloxacin is one of the new quinolone antibacterial agents. The branched-chain of it is the most important part of the efficacy, which has the decisive influence to the pharmacology activity. Synthetic methods of the branched-chain have been reviewed, these methods have been analyzed and compared with each other, and the merits and defects of each method have been presented. It＇s better to use oxidation methods to synthesize the branched-chain then non- oxidation methods with milder conditions, low in the pollution of the environment and an overall yield of 39.6%. In the methods, it is suitable to use borohydride-chlorizated salts when intermediate 3 （4-cyano- 1-（N-t-butoxycarbony）pyrrolidin-3-keton） is reduced to 4 （4-aminomethyl- 1-（N-t-butoxycarbony）pyrrolidin-3-alcohol ） and to use Jones reagent when intermediate 5＇ （4-（N-t-butoxycarbony）aminomethyl- 1-（N-t-butoxycarbony）pyrrolidin-3-alcohol） is oxidezed to 6 （4-（N-t-butoxycarbony）aminomethyl- 1-（N-t-butoxycarbony）pyrrolidin-3-keton） with high yield, good purity and easy operation.
出处
《广州化学》
CAS
2011年第4期69-74,共6页
Guangzhou Chemistry
基金
常州工程职业技术学院科研基金立项课题(KJY2010-11)
关键词
喹诺酮
吉米沙星支链
合成
quinolones
gemifloxacin branched-chain
synthesis
