HIV蛋白酶抑制剂利托那韦的合成工艺改进  

Improved synthesis of HIV protease inhibitor ritonavir

作　　者：白跃飞 周宏 吴晓璟 于河舟 周凯 

机构地区：[1]东北制药集团股份有限公司,辽宁沈阳110027

出　　处：《中国药物化学杂志》2018年第1期29-33,共5页Chinese Journal of Medicinal Chemistry

基　　金：辽宁百千万人才工程项目(【2015】2号);辽宁省博士启动基金项目(201501139);沈阳市科学技术计划项目(F16-179-9-00)

摘　　要：目的改进HIV蛋白酶抑制剂利托那韦的合成工艺。方法以L-苯丙氨酸为原料,经三苄基保护、还原性缩合及格氏试剂偶联、α,β-不饱和酮还原、Boc保护、选择性脱苄基、缩合、脱Boc基、再次缩合得到利托那韦。结果与结论目标化合物的结构经~1H-NMR、^(13)C-NMR和MS谱确证,总收率为73.3%(以L-苯丙氨酸计),HPLC法测定纯度达99.8%。与文献报道的工艺相比,该路线操作简易、成品质量好、生产成本较低,有利于工业化生产。The synthetic route for the preparation of HIV protease inhibitor ritonavir was improved with a series of successive steps,including the protection of L-phenylalanine by tribenzylation, reductive condensa- tion, coupled reaction by Grignard reagent, reduction reaction of α ,β-unsaturated ketone, Boc protection, and deprotection of selective benzyl, followed by condensation, Boc deprotection as well as recondensation. The structure of the obtained product was further characterizated by 1H-NMR, 13C-NMR and MS. The overall yield of the product could be achieved as high as 73.3% in this way ,together with a high purity of 99.8%, detected and confirmed by HPLC. Compared with traditional technologies, this low-cost synthetic approach for high-quality product was operated easily, which was suitable and promising for industrial production.

关 键 词：利托那韦 HIV蛋白酶 抑制剂 工艺改进 

分 类 号：R914[医药卫生—药物化学]