洛匹那韦/利托那韦关键中间体的合成  

Synthesis of Key Intermediates of Lopinavir/Ritonavir

作　　者：何彩玉[1] 王曙光[1] 丁时磊[1] 汪玉玲[1] 朱迪[1] 江玉琨 HE Cai-yu;WANG Shu-guang;DING Shi-lei;WANG Yu-ling;ZHU Di;JIANG Yu-kun(Department of Medicine,Chuzhou City Vocational College,Chuzhou 239000,China)

机构地区：[1]滁州城市职业学院医学院,安徽滁州239000

出　　处：《宜春学院学报》2023年第6期17-21,共5页Journal of Yichun University

基　　金：安徽省质量工程项目(编号:2021jxtd204);滁州城市职业学院科研项目(编号:2022zkyb01,2021bmzx02);滁州城市职业学院质量工程项目(编号:2020gzzy03,2020jyxm02)。

摘　　要：目的:洛匹那韦/利托那韦关键中间体的合成工艺优化。方法:以(2S)-5-氨基-2-(N,N-二苄基)氨基-3-氧代-1,6-二苯基己-4-烯为起始原料,通过两步还原反应、叔丁氧羰基(Boc)保护反应、钯碳还原反应以及丁二酸拆分反应等4步,获得了(2S,3S,5S)-3-羟基-2-氨基-5-(叔丁氧羰基)氨基-1,6-二苯基正己烷丁二酸盐。结果:合成了高光学纯度的洛匹那韦/利托那韦关键中间体——(2S,3S,5S)-3-羟基-2-氨基-5-(叔丁氧羰基)氨基-1,6-二苯基正己烷丁二酸盐(总收率48%,纯度>99%)。结论:获得了一条高效、简洁的洛匹那韦/利托那韦关键中间体合成工艺路线,有望应用于工业化生产。Objective:To optimize the synthesis of key intermediates of lopinavir/ritonavir.Methods:(2S,3S,5S)-3-hydroyl-2-amino-5-(tert-butyryl)amino-1,6-diphenyln-hexane succinate was synthesized via four steps including two-step reduction reaction,tert-butyric oxide(Boc)protection reaction,palladium carbon reduction reaction and succinic acid resolution reaction from(2S)-5-amino-2-(N,N-dibenzyl)amino-3-oxygen-1,6-diphenylself-4-ene.Results:The key intermediates of lopinavir/ritonavir——(2S,3S,5S)-3-hydroyl-2-amino-5-(tert-butyryl)amino-1,6-diphenyln-hexane succinate was synthesized with high purity and high yield(overall yield 48%,purity>99%).Conclusion:An efficient and concise synthesis route of key intermediates of lopinavir/ritonavir is available,which makes it suitable for industrial production.

关 键 词：洛匹那韦 利托那韦 HIV蛋白酶抑制剂 关键中间体 合成工艺 

分 类 号：R914.5[医药卫生—药物化学]