Chin. J. Org. Chem. ›› 2008, Vol. 28 ›› Issue (08): 1398-1403. Previous Articles     Next Articles

Original Articles

酶催化拆分制备手性2-氯-1-(2,4-二氟苯基)乙醇及 光学活性抗真菌药物的合成

王明慧a,b ; 杨 光a ; 杨立荣*,a   

  1. (a浙江大学化学工程与生物工程学系 杭州 310027)
    (b青岛科技大学化学与分子工程学院 青岛 266042)
  • 收稿日期:2007-08-09 修回日期:2008-01-18 发布日期:2008-08-18
  • 通讯作者: 杨立荣

Preparation of Chiral 2-Chloro-1-(2,4-difluorophenyl)ethanol by Lipase-Catalyzed Resolution and Synthesis of Optically Active Antifungal Drug

WANG, Ming-Hui a,b; YANG, Gang a ; YANG, Li-Rong*,a   

  1. (a Department of Chemical and Biochemical Engineering, Zhejiang University, Hangzhou 310027)
    (b College of Chemistry and Molecular Engineering, Qingdao University of Science & Technology, Qingdao 266042)
  • Received:2007-08-09 Revised:2008-01-18 Published:2008-08-18
  • Contact: YANG, Li-Rong

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