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

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% eel, 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. (C) 1998 Elsevier Science Ltd. All rights reserved.