HIV蛋白酶抑制剂硫酸阿扎那韦的合成  

Synthesis of HIV protease inhibitors atazanavir sulfate

作　　者：白跃飞 皮昌桥 吴晓璟 刘举[2] 周鹏 周凯 BAI Yue-fei;PI Chang-qiao;WU Xiao-jing;LIU Ju;ZHOU Peng;ZHOU Kai(Northeast Pharmaceutical Group Co.,Ltd.,Shenyang 110027,China;College of Pharmacy,Liaoning University,Shenyang 110036,China)

机构地区：[1]东北制药集团股份有限公司,沈阳110027 [2]辽宁大学药学院,沈阳110036

出　　处：《中国新药杂志》2018年第15期1798-1802,共5页Chinese Journal of New Drugs

基　　金：辽宁百千万人才工程资助项目([2015]2);辽宁省博士启动基金资助项目(201501139);沈阳市科学技术计划资助项目(F16-179-9-00)

摘　　要：目的:对硫酸阿扎那韦的合成工艺进行研究。方法:以(2S,3S)-3-叔丁氧羰基氨基-1-氯-2-羟基-4-苯基丁烷为起始原料,经SN2取代、分子内重排、N-Boc保护、环合、环氧环开环胺解、脱Boc、成盐并经碱性游离、缩合和离子交换反应制得硫酸阿扎那韦。结果:目标化合物的结构经1H NMR、13C NMR和MS谱确证,总收率为61.2%(以起始原料计),HPLC测定纯度达99.8%。结论:该工艺所用原料易得、操作简便、收率较高、成品质量好,适合工业化生产。Objective： To study the synthetic technology of atazanavir sulfate. Methods： Tert-butyl（2 S,3 S）-4-chloro-3-hydroxy-1-phenylbutan-2-ylcarbamate was used as the starting material and treated by SN2 reaction,intramolecular rearrangement, Boc-protection, cyclization, epoxide ring aminolysis, followed by deprotection,salifying,neutralization,condensation,and ion exchange resin reaction to get the target product. Results： The structure of atazanavir sulfate with an overall yield of 61. 2% by starting material meter was confirmed by1 H-NMR,13 C-NMR and MS,and the purity was 99. 8% estimated by HPLC. Conclusion： This synthetic process is available raw materials,easy operation,high yield,and has good quality production. In conclusion,it has feasibility of industrial production.

关 键 词：硫酸阿扎那韦 HIV蛋白酶抑制剂 合成 

分 类 号：R914.5[医药卫生—药物化学]