Optically Active Antifungal Azoles. II. Synthesis and Antifungal Activity of Polysulfide Derivatives of (2R,3R)-2-(2,4-Difluorophenyl)-3-mercapto-1-(1H-1,2,4-triazol-1-yl)-2-butanol.
作者:Akihiro TASAKA、Norikazu TAMURA、Yoshihiro MATSUSHITA、Ryogo HAYASHI、Kenji OKONOGI、Katsumi ITOH
DOI:10.1248/cpb.41.1043
日期:——
In an effort to find potent antifungal agents, a variety of optically active triazole derivatives with a polysulfide structure, 3, 4 and 5, were prepared and evaluated for antifungal activity against Candida albicans in vitro and in vivo. The symmetrical polysulfides 3 (m=2-4) were obtained by an oxidative coupling reaction of (2R, 3R)-2-(2, 4-difluorophenyl)-3-mercapto-1-(1H-1, 2, 4-triazol-1-yl)-2-butanol (1) or by the treatment of its thiocarbonate derivative 8 with potassium tert-butoxide. The unsymmetrical disulfides 5 were synthesized by the reaction of the thiol 1 with Bunte salts 11 or the thiosulfinate 12 or by the reaction of the thiocarbonate 8 with various thiols 13. All of these polysulfides showed potent antifungal activity against candidosis in mice.
为了寻找有效的抗真菌药物,我们制备并评估了一系列具有多硫化物结构的具有光学活性的三唑衍生物3、4和5,在体外和体内对白色念珠菌的抗真菌活性。通过对(2R, 3R)-2-(2, 4-二氟苯基)-3-巯基-1-(1H-1, 2, 4-三唑-1-基)-2-丁醇(1)的氧化偶联反应或其硫代碳酸酯衍生物8与叔丁醇钾的处理,得到了对称的多硫化物3(m=2-4)。通过对硫醇1与Bunte盐11或硫代亚磺酸盐12的反应,或通过硫代碳酸酯8与各种硫醇13的反应,合成了不对称二硫化物5。所有这些多硫化物都显示出对小鼠念珠菌病有强大的抗真菌活性。