Determination of absolute configuration of a metabolite (−)-hydroxyhexamide from acetohexamide, syntheses of (−)- and (+)-hydroxyhexamides and (−)- and (+)-acetoxyhexamides

Abstract

Enantioselective acetylation of (±)-4-(1-hydroxyethyl)benzenesulfonamide 6 with `Acylase I' (No. A 2156) from Aspergillus melleus in the presence of vinyl acetate gave ( R)-4-(1-acetoxyethyl)benzenesulfonamide 7 (98% ee) and ( S)- 6 (98% ee). Both ( S)- 6 and ( R)- 7 were individually converted to the ( S)-hydroxyhexamide 2 (>99% ee) and ( R)-hydroxyhexamide 2 (>99% ee), respectively. The absolute configuration of a metabolite (−)-hydroxyhexamide 2 from acetohexamide 1 was found to be S based on unequivocal chemical methods including X-ray analysis.