抗结核候选药物PA-824的合成工艺优化  

Process Improvement on The Synthesis of Anti-tuberculosis Candidate PA-824

作　　者：张静静[1,2] 姚明 杨森 熊航行 刘生鹏 ZHANG Jing-jing;YAO Ming;YANG Sen;XIONG Hang-xing;LIU Sheng-peng(School of Chemical Engineering and Pharmacy,Wuhan Institute of Technology,Wuhan 430205,China;College of Chemical Engineering and Pharmacy,Jingchu University of Technology,Jingmen 448000,China)

机构地区：[1]武汉工程大学化工与制药学院,湖北武汉430205 [2]荆楚理工学院化工与药学院,湖北荆门448000

出　　处：《合成化学》2019年第12期991-995,共5页Chinese Journal of Synthetic Chemistry

基　　金：湖北省自然科学基金资助项目(2016CFB149);湖北省教育厅优秀中青年科技创新团队计划项目(T201719)

摘　　要：对抗结核候选药物PA-824的合成方法进行了优化。以4-硝基咪唑为原料,依次经亲核开环氧反应、氧烷基化反应和脱酯基反应制得(S)-3-(4-硝基-1 H-咪唑-1-)-2-[(4-三氟甲氧基)苄氧基]丙烷-1-醇(3);3在铜催化下发生分子内碳氢键活化烷氧化反应合成PA-824,总收率达到56.5%,其结构经1H NMR,13CNMR和MS(ESI)确证。The synthetic route of anti-tuberculosis candidate PA-824 was improved.(S)-3-(4-nitro-1 H-imidazol-1-yl)-2-{[4-(trifluoromethoxy)benzyl]oxy}propan-1-ol(3)was synthesized from 4-nitroimidazole via nucleophilic ring opening reaction,oxyalkylation and deesterification reaction,respectively.Then 3 was subjected to intramolecular C—H activated alkoxylation to obtain PA-824,under catalysis of copper.The total yield was up to 56.5%.The structure was confirmed by 1 H NMR,13 C NMR and MS(ESI).

关 键 词：抗结核药 PA-824 4-硝基咪唑 碳氢键活化 药物合成 工艺改进 

分 类 号：O621.3[理学—有机化学] R914.5[理学—化学]