Key chiral intermediates (R)- and (S)-2-chloro-1-(2,4-difluorophenyl)ethanols were prepared by kinetic resolution of the racemic mixture with Pseudomonas stutzeri lipase-catalyzed irreversible transesterification yielding (R)-alcohol and (S)-acetate, the (R)-alcohol with 95.8% ee and (S)-alcohol with 94.5% ee were obtained. And four optically active 2,4-difluoro-1-[1-(p-chlorobenzyloxy)-2-(1-imidazolyl)]ethyl- benzene nitric acid compounds possessing antifungal activity were synthesized. The results of antifungal tests in vitro by a method of filter paper disk diffusion showed that (R)-5a and (R)-5b had excellent antifungal activity against various candida species, and equal to fluconazole. Especially, 5a, 5b and their two optically active isomers have excellent antifungal efficacy against Aspergillus fumigatus that is resistant to fluconazole, moreover their (R)-isomers are more potent than their (S)-isomers and the racemate.

Key words: lipase-catalyzed resolution, chirality, antifungal drug, 2-chloro-1-(2,4-difluorophenyl)ethanol