Discovery of New Antifungal Polyketides Cladrioides A–N against Phytopathogenic Fungi from Cladosporium cladosporioides LD-8

During the search for natural fungicides, 14 new australifungin analogues cladrioides A–S (1–14) and two known ones (15 and 16) were obtained from Cladosporium cladosporioides LD-8. Their structures were elucidated by comprehensive analysis of NMR and HRESIMS data, as well as ECD calculations. Compounds 1 and 2 possess a novel 6/6/5-fused tricyclic scaffold. Most of the compounds exhibited remarkable antifungal activities against the tested phytopathogenic fungi. Among them, compounds 7, 10, and 16 showed excellent activities with IC₅₀ values ranging from 1.71 to 16.63 μg/mL. Their inhibitory activities against A. brassicicola and A. alternata were higher than that of the commercial fungicide hymexazol. Compound 16 displayed potent in vivo antifungal activity against A. solani at 100 μg/mL with an inhibitory rate of 96.82%. The structure–activity relationship of antifungal australifungin analogues was analyzed for the first time. Therefore, our study provides promising candidates for the development of new fungicides for plant protection.