洛匹那韦/利托那韦关键中间体的合成

Synthesis of Key Intermediates of Lopinavir/Ritonavir

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.