Liao Y W, Li H X
Department of Chemistry, Second Military Medical University, Shanghai.
Yao Xue Xue Bao. 1993;28(1):22-7.
In an effort to investigate the relationship between stereochemistry and antifungal activity of the antimycotic agents, optically active econazole and miconazole were first enantioselectively synthesized. The key step was the enantioselective reduction of 2-chloro-1-(2,4-dichlorophenyl) ethanone catalyzed by chiral oxazaborolidine. Preliminary biological tests showed that (R)-(-)-econazole and (R)-(-)-miconazole were more active than the (S)-isomer and racemates against common pathogenic fungi such as Candida albicans, Trichophyton rubrum, T. gypseum, Microsporum lanosum and Aspergillus flavus in vitro.
为了研究抗真菌药物的立体化学与抗真菌活性之间的关系，首先对光学活性的益康唑和咪康唑进行了对映选择性合成。关键步骤是在手性恶唑硼烷催化下对2-氯-1-(2,4-二氯苯基)乙酮进行对映选择性还原。初步生物学试验表明，在体外，(R)-(-)-益康唑和(R)-(-)-咪康唑对白色念珠菌、红色毛癣菌、石膏样毛癣菌、羊毛状小孢子菌和黄曲霉等常见致病真菌的活性比(S)-异构体和外消旋体更强。
