Study On The Synthesis Of The Core Unit Of Ritonavir And Lopinavir

Ritonavir and Lopinavir,human immunodeficiency virus(HIV)protease inhibitors(PIs),are widely used in clinic treatment of acquired immuno deficiency syndrome(AIDS).Especially in the "cocktail"therapy treatment,when combine with other anti-virus drugs,ritonavir can significantly increase the enteral absorption,decreas side effects and improve the patients' life quality and survival rate.So it's important to study on the synthesis of Ritonavir and Lopinavir. (2S,3S,5S)-2,5-diamino-3-hydroxy-1,6-diphenyl hexane is the important intermidate and key problem for synthesis of Ritonavir and Lopinavir.(2S,3S,5S)-2,5-diamino-3-hydroxy-1,6- diphenylhexane was retrosynthe -tic analysised and synthesized,and a new convenient enantioselective synthesis route was investigated.(2S)-2-(benzyloxycarbonyl)amino phenylpropyl aldehyde was synthesized from L-Phenylalanine after oxidized and reduced(three steps total yield was 70%). When using market sold N-Cbz-L-Phe-OMe as starting material, (2S)-2-(benzyloxycarbonyl)amino phenylpropyl aldehyde could be directly synthesized after reduced by only one step(total yield was 88%).Then, (2S,3R,4R,5S)-2,5-di[(benzyloxycarbonyl)amino]-3-hydroxy-1,6-diphenylheane was obtained through stereoselective homopinacolcoupling reaction.Finally,the target compound was obtained through a 1,2-cycle sulfate intermediate compound which could selectively release one hydroxy.The structure of every step products and the target compound obtained in this paper were determined and analysised by NMR,Hight Resolution Accurate Mass Measurement/Elemental Composition,etc.The total yield was 40%based on N-Cbz-L-Phe-OMe as the starting material.