Stereoselective synthesis of non symmetric dihydroxyethylene dipeptide isosteres via epoxy alcohols derived from alpha-amino acids

Abstract

(1R,2R,3S,4S)-4-Amino-3-hydroxy-1,2-epoxybutanes, accessible in four steps from L-aminoesters, react regio- and stereoselectively with diethyl aluminum cyanide to give (1R,2S,3S,4S)-4-amino-2,3-dihydroxynitriles. Hydrolysis yields hydroxylactones equivalent to 2,3-dihydroxy-4-aminoacids. The sequence provides a novel approach to dihydroxyethylene isosteres potentially useful for new HIV-protease inhibitors.