Diastereoselective synthesis of (3r, 3as, 6ar)-hexahydrofuro [2, 3-b] furan-3-Yl (2r, 3r)-4-(4-amino-N-isobutylphenylsulfo- namido)-3- hydroxy-1-phenylbutan-2-ylcarbamate (diastereomer of darunavir)

摘要

(3R,3aS,6aR)-Hexahydrofuro[2,3-b]furan-3-yl(2S,3S)-4-(4-amino-N-isobutylphenylsulfonamido) -3-hydroxy-1-phenylbutan-2-ylcarbamate 4 was synthesised from 4-amino-N-((2S,3S)-3-amino- 2-hydroxy-4-phenylbutyl)-N-isobutylbenzenesulfo- namide 3 via N-protected amino alcohol intermeidate 2 while (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl (2S,3R)-4-(4-amino-Nisobutylphenylsulfonamido)- 3-(((3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yloxy)carbonyloxy)- 1-phenylbutan-2-yl carbamate 6 was prepared from (3R, 3aS, 6aR)-hexahydrofuro [2, 3-b] furan-3-yl 4-nitrophenyl carbonate 3a. The desired drug 4 was obtained with 99 % diastereoselectivity. The spectroscopic analyses performed by NMR, LCMS, UV–Vis, SOR and FT-IR.