Synthesis and Antifungal Activities of Carabrol Ester Derivatives

Thirty-eight new ester derivatives of carabrol were designed, synthesized, and characterized by H-1 and C-13 NMR and HR-ESI-MS. Their antifungal activities against the fungal pathogen Colletotrichum lagenarium were evaluated using a spore germination assay. Of these 38 ester derivatives, 16 showed higher antifungal activity than that of carabrol and 7 showed higher antifungal activity than that of carabrone. It was found that the C-4 position of carabrol was a key position involving its antifungal activity, which showed the variation of 50% inhibition concentration (IC50) from 2.70 to 52.33 mu g/mL. When substituted by the phenyl ring, the ester derivatives with electron-attracting groups showed higher activity than those with electron-donating ones. Two ester derivatives, carabryl 4-cynaobenzoate (II-17, IC50 2.70 mu g/mL) and carabryl 4-isopropylbenzoate (II-27, IC50 2.82 mu g/mL), showed only slightly lower antifungal activity than that of the positive control chlorothalonil (IC50 0.87 mu g/mL) and have been identified as promising leads for development of new environmentally friendly fungicides.