Study On The Synthetic Process Of Amprenavir Intermediate

(1S,2R)-3-[N-(4-Aminophenylsulfonyl)-N-ispropylamino]-1-benzyl-2-hydroxypropylcarbamic acid (3S)-tetrahydro-3-furanyl ester,is the 5th generation of anti-retroviral protease inhibitors developed by Glaxo-Smith. It was first saled in the U.S. and Japan In May 1999. Amprenavir is an important clinical drug for the treatment of AIDS, and is also the Second-generation protease inhibitor peptide drug .Based on references, the classification of Anti-AIDS drugs, the history and present situation of protease inhibitors were reviewed in this paper. The synthetic routes and methods of the protease inhibitors of Amprenavir intermediate were summarized.Tert-butyl((S)-1-((R)-oxiran-2-yl)-2-phenylethyl)carbamate was used as starting material. The target product can be obtained by Ring opening reaction used Iso-Butylamine,N-Sulfonation reaction,Deprotection,Condensation reaction used (S)-2,5-dioxopyrrolidin-1-yl (tetrahydrofuran-3-yl) carbonate. The total yield is up to 74.1 %. This paper was also researched on the catalytic asymmetric synthesis of (S)-3 - hydroxy-tetrahydrofuran. It was 4-chlorobutanal as the raw material, reacted with nitrosobenzene, reducted by NaBH4, intramolecular cyclization to get the target product.This paper researched on the preferable technological conditions of Amprenavir intermediate, such as such as reactant proportion, solvent, reaction times, etc, have been obtained. The structure of the target compound was confirmed by NMR and MS. The optimum synthetic route of the Amprenavir has many advantages such as easy operation, low cost and was suitable for industrial production.