OPTICALLY-ACTIVE ANTIFUNGAL AZOLES .1. SYNTHESIS AND ANTIFUNGAL ACTIVITY OF YL)-3-MERCAPTO-1-(1H-1,2,4-TRIAZOL-1-YL)-2-BUTANOL AND ITS STEREOISOMERS

yl)-3-mercapto-1-(1H-1,2,4-triazol-1-yl)-2-butanol [(2R,3R)-71 and its stereoisomers [(2S,3R)-, (2S,3S)- and (2R,3S)-7] were prepared from t he optically active oxiranes 6 by a newly developed ring-opening react ion and evaluated for antifungal activity. The thiol (2R,3R)-7 showed extremely potent antifungal activity in vitro and in vivo. The optical ly active.oxirane (2R,3S)-6, a useful intermediate for the synthesis o f sulfur-containing antifungal azoles 5, was synthesized from methyl ( R)-lactate [(R)-8] via eight steps in a stereocontrolled manner. The k ey step in the synthesis is the Grignard reaction of an amide derivati ve [(R)-12a] of (R)-lactic acid with 2,4-difluorophenyl-magnesium brom ide (13).