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

Abstract

(2R,3R)-3-Azolyl-2-(substituted phenyl)-l-(lH-l,2,4-triazol-l-yl)-2-butanols (III) were prepared from (2R,3S)-3-methyl-2-(substituted phenyl)-2-(lH-l,2,4-triazol-l-yl)methyloxiranes (21a—f) by a ring-opening reaction with 1H-1,2,3-triazole and lH-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 l-[(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-(lH-l,2,3,-triazol-l-yl)-(IIIa) and 3-(2H-2-tetrazolyl)-2-butanol (Hid) derivatives showed strong protective effects against candidosis in mice. © 1995, The Pharmaceutical Society of Japan. All rights reserved.