Three new polyketide-derived natural products, cladobotric acids G-I (<b>1</b>-<b>3</b>), and six known metabolites (<b>4</b>, <b>5</b>, <b>8</b>-<b>11</b>) were isolated from fermentation of the fungus <i>Cladobotryum</i> sp. grown on rice. Their structures were elucidated by extensive spectroscopic methods. Two metabolites, cladobotric acid A (<b>4</b>) and pyrenulic acid A (<b>10</b>), were converted to a series of new products (<b>12</b>-<b>20</b>) by semisynthesis. The antibacterial activities of all these compounds were investigated against the Gram-positive pathogen <i>Staphylococcus aureus</i> including methicillin-susceptible (MSSA), methicillin-resistant and vancomycin-intermediate (MRSA/VISA), and heterogeneous vancomycin-intermediate (hVISA) strains. Results of these antibacterial assays revealed structural features of the unsaturated decalins important for biological activity.