3-氯代亚甲基色满-4-酮类化合物的设计、合成及体外抗真菌活性研究

Design, synthesis and in vitro antifungal activity of 3-substituted-methylenechroman-4-ones

摘要:
本文以取代苯酚为原料, 经微波条件下的取代反应和多聚磷酸中进行的环合反应制备了取代色满酮, 取代色满酮与甲酸乙酯的缩合产物经氯化反应制备了3-氯代亚甲基色满-4-酮类化合物, 共合成了10种未见文献报道的新化合物。化合物结构经质谱和核磁共振氢谱进行了确证, 并且采用二倍稀释法对目标化合物的体外抗真菌活性进行了测试, 结果表明它们具有很好的体外抗真菌活性, 其中化合物4c、4e、4g和4h对石膏样小孢子菌的MIC值为1 μg·mL⁻¹, 高于对照药氟康唑和两性霉素B, 具有进一步研究价值。

Abstract:
Substituted phenols as the starting materials were transformed into substituted chromanones by substitution reaction and cyclization reaction, and then 3-(hydroxymethylene)chroman-4-ones were synthesized from substituted chromanones by condensation reaction; at last, the target compounds were synthesized from 3-(hydroxymethylene)chroman-4-ones by chlorination reaction. Their structures were confirmed by ¹H NMR and MS. The antifungal activity of the target compounds in vitro was measured by consecutive double dilution, and the result of antifungal experiment indicated that the target compounds had good antifungal action on most fungi tested in vitro. The MIC value of compounds 4c, 4e, 4g and 4h on M. gypseum is 1 μg·mL⁻¹, better than fluconazole and amphotericin B.