Optically Active Antifungal Azoles. II. Synthesis and Antifungal Activity of Polysulfide Derivatives of (2R,3R)-2-(2,4-Difluorophenyl)-3-mercapto-1-(1H-1,2,4-triazol-1-yl)-2-butanol.

• DOI: 10.1248/cpb.41.1043
• Publication Date: 2011-12-08T04:42:42Z
• Authors: Akihiro TASAKA; Norikazu TAMURA; Yoshihiro MATSUSHITA; Ryogo HAYASHI; Kenji OKONOGI; Katsumi ITOH
• Keywords: Azoles; Antifungal Agents; Magnetic Resonance Spectroscopy; Spectrophotometry, Infrared; Candidiasis; Stereoisomerism; Triazoles; 01 natural sciences; 0104 chemical sciences; 3. Good health; Mice; Structure-Activity Relationship; Candida albicans; Animals; Sulfhydryl Compounds; Oxidation-Reduction; Chromatography, High Pressure Liquid

In an effort to find potent antifungal agents, a variety of optically active triazole derivatives with a polysulfide structure, 3, 4 and 5, were prepared and evaluated for antifungal activity against Candida albicans in vitro and in vivo. The symmetrical polysulfides 3 (m = 2-4) were obtained by an oxidative coupling reaction of (2R,3R)-2-(2,4-difluorophenyl)-3-mercapto-1-(1H-1,2,4-triazol-1-yl )-2-butanol (1) or by the treatment of its thiocarbonate derivative 8 with potassium tert-butoxide. The unsymmetrical disulfides 5 were synthesized by the reaction of the thiol 1 with Bunte salts 11 or the thiosulfinate 12 or by the reaction of the thiocarbonate 8 with various thiols 13. All of these polysulfides showed potent antifungal activity against candidosis in mice.