Optically Active Antifungal Azoles. IV. Synthesis and Antifungal Activity of (2R, 3R)-3-Azolyl-2-(substituted phenyl)-1-(1H-1, 2, 4-triazol-1-yl)-2-butanols

Abstract

(2R, 3R)-3-Azolyl-2-(substituted phenyl)-1-(1H-1, 2, 4-triazol-1-yl)-2-butanols (III) were prepared from (2R, 3S)-3-methyl-2-(substituted phenyl)-2-(1H-1, 2, 4-triazol-1-yl)methyloxiranes (21a-f) by a ring-opening reaction with 1H-1, 2, 3-triazole and 1H-tetrazole and evaluated for antifungal activity against Candida albicans in vitro and in vivo. The optically active oxiranes (21a-f), which serve as the key synthetic intermediates, were synthesized from 1-[(2R)-2-(3, 4, 5, 6-tetrahydro-2H-pyran-2-yl)oxypropanoyl]morpholine (24) and substituted phenylmagnesium bromide (23) via six steps in a stereocontrolled manner. The 3-(1H-1, 2, 3, -triazol-1-yl)-(IIIa) and 3-(2H-2-tetrazolyl)-2-butanol (IIId) derivatives showed strong protective effects against candidosis in mice.