Optically Active Antifungal Azoles. VI. Synthesis and Antifungal Activity of N-((1R,2R)-2-(2,4-Difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl)-N'-(4-substituted phenyl)-3(2H,4H)-1,2,4-triazolones and 5(1H,4H)-tetrazolones.

• DOI: 10.1248/cpb.44.314
• Publication Date: 2011-12-08T04:44:54Z
• Authors: Tomoyuki KITAZAKI; Norikazu TAMURA; Akihiro TASAKA; Yoshihiro MATSUSHITA; Ryogo HAYASHI; Kenji OKONOGI; Katsumi ITOH
• Keywords: Benzothiadiazines; Trifluoromethanesulfonate; Triazole

A new series of optically active antifungal azoles, N-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-tria zol-1- yl)propyl]-N'-(4-substituted phenyl)-3(2H,4H)-1,2,4-triazolones (1,2) and 5(1H,4H)-tetrazolones (3), were prepared from the triflate derivative (1S)-1-[(2R)-2-(2,4-difluorophenyl)-2-oxiranyl]ethanol (13) by an SN2 displacement reaction with anion azolone (17-19) subsequent ring-opening 1H-1,2,4-triazole. The oxiranylethanol 13 was synthesized methyl (R)-lactate in a stereo-controlled manner. azolones 1-3 showed potent activities vitro vivo.