Research on the Synthesis of the Chiral Intermediate of a New Anti-HIV Drug Fosamprenavir
|Course||Textile Chemistry and Dyeing and Finishing Engineering|
|Keywords||Fosamprenavir AIDS HIV Protease inhibitors L-phenylalanine Chiral Asymmetric reduction Synthesis|
Fosamprenavir (Fosamprenavir, GW433908, trade name Lexiva ) is jointly developed by GSK and Vertex efficient treatment of AIDS protease inhibitor ( PI ) . Fosamprenavir is a prodrug of the protease inhibitor Amprenavir , highly water-soluble low reactive phosphate , medication , there are good prospects for development . This product has been formally approved by the FDA in October 2003 in the United States . ( 2R , 3S ) -3 - ( t-butoxy- carbonyl ) - amino -2 - hydroxy-1 - ( isobutyl- nitrobenzenesulfonyl ) - amino-4 - phenyl- butane is synthesized fosamprenavir the key intermediate , structural compound is a hydroxy- ethyl- amine (HEA) having two chiral centers . The papers in the literature on the basis of the design of the route to L-phenylalanine as the starting material was successfully synthesized the key intermediate , and its synthesis process research and improvement . Among them, the raw material has a wide source , suitable for large-scale production . L-phenylalanine amino-protecting , nucleophilic replace , restore, nucleophilic addition , condensation six-step reaction to 47 % of the total yield of product was obtained , higher than the existing synthetic route . The entire route fewer steps , mild reaction conditions , reagents and catalysts is cheap and easy to get , easy product separation and purification , high yield . In particular , is one of the key steps - alpha - nitro ketone asymmetric reduction , the single configuration product obtained in 77 % yield , and ( 2R , 3S ) and ( 2R , 3S ) two diastereoisomers isomer ratio from 74:26 to 85:15 . The final product and all intermediates been recognized in the NMR analysis .