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

During the search for natural fungicides, 14 new australifungin analogues cladrioides A-S (<b>1</b>-<b>14</b>) and two known ones (<b>15</b> and <b>16</b>) were obtained from <i>Cladosporium cladosporioides</i> LD-8. Their structures were elucidated by comprehensive analysis of NMR and HRESIMS data, as well as ECD calculations. Compounds <b>1</b> and <b>2</b> 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 <b>7</b>, <b>10</b>, and <b>16</b> showed excellent activities with IC₅₀ values ranging from 1.71 to 16.63 μg/mL. Their inhibitory activities against <i>A</i>. <i>brassicicola</i> and <i>A</i>. <i>alternata</i> were higher than that of the commercial fungicide hymexazol. Compound <b>16</b> displayed potent <i>in vivo</i> antifungal activity against <i>A</i>. <i>solani</i> 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.