Total synthesis and biological evaluation of an antifungal tricyclic o-hydroxy-p-quinone methide diterpenoid.

A convergent route has been developed to synthesize an antifungal tricyclic o-hydroxy-p-quinone methide diterpenoid and analogs. The Li/naphthalene mediated reductive alkylation was employed for coupling β-cyclocitral and the corresponding benzyl chloride while the BBr3–mediated one-pot bis-demethylation and intramolecular Friedel Crafts alkylation was used to assemble the tricyclic molecular skeleton. The structure-activity relationship of the diterpenoid was assessed based on anti-proliferation assays of the natural product and analogs against strains of pathogenic yeasts and filamentous fungi.

已经开发出一种收敛性合成路线来合成一种抗真菌的三环邻羟基对苯醌甲基化物二萜类化合物及其类似物。采用锂/萘介导的还原烷基化反应将β-环柠檬醛与相应的苄基氯偶联，同时使用BBr₃介导的一锅法双脱甲基化和分子内傅克烷基化反应来构建三环分子骨架。基于该天然产物及其类似物对致病性酵母和丝状真菌菌株的抗增殖试验，评估了二萜类化合物的构效关系。