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

Abstract

The (2S, 3S)-, (2R, 3S)- and (2S, 3R)-stereoisomers of (2R, 3R)-3-azolyl-2-(substituted phenyl)-1-(1H-1, 2, 4-triazol-1-yl)-2-butanols [(2R, 3R)-1a-d] were prepared and evaluated for antifungal activity against Candida albicans in vitro and in vivo to clarify the relationships between stereochemistry and biological activities. The results revealed that the in vitro antifungal activity in each set of the four stereoisomers [(2R, 3R)-, (2S, 3S)-, (2R, 3S)- and (2S, 3R)-1a-d] definitely paralleled the in vivo antifungal activity against candidosis in mice, and the order of potency was (2R, 3R)»(2R, 3S)≥(2S, 3S)≥(2S, 3R).In addition, the four stereoisomers in each set were assessed for sterol biosynthesis-inhibitory activities in C. albicans and rat liver. The (2R, 3R)-isomer was found to exert a strong and selective inhibitory effect on the sterol synthesis in C. albicans as compared with that in rat liver.