Synthesis and in vitro antifungal activities of novel triazole antifungal agent CS-758

Synthesis and in vitro antifungal activities of a novel triazole antifungal agent CS-758 (former name, R-120758) are described. The minimum inhibitory concentrations (MICs) of a series of dioxane-triazole compounds related to R-102557 were examined. Variation of the length of the chain between the d ioxane ring and the phenyl ring revealed that the linkage with two double b onds is the most preferable. When a cyano group was introduced to the C4 po sition on the benzene ring, MICs improved further. A fluorine atom was intr oduced to obtain CS-758. The MICs of CS-758 surpassed those of fluconazole and itraconazole against Candida, Aspergillus and Cryptococcus species. The precursor (E,E)-aldehyde was synthesized stereoselectively from 3-fluoro-4 -methylbenzonitrile using the Horner-Wadsworth-Emmons reaction.