New Polyketide Congeners with Antibacterial Activities from an Endophytic Fungus Stemphylium globuliferum 17035 (China General Microbiological Culture Collection Center No. 40666)

Four new polyketides, heterocornol Y (<b>1</b>), stemphyindan (<b>2</b>), pestalospirane C (<b>3</b>), and stemphyspyrane (<b>4</b>), along with five known ones (<b>5</b>-<b>9</b>) were isolated from the endophytic fungus <i>Stemphylium globuliferum</i> 17035 (SG17035) based on the One Strain Many Compounds (OSMAC) strategy allied with an LC-MS approach. These structures were elucidated through extensive spectroscopic analyses, single-crystal X-ray diffraction, and ¹³C NMR-DP4 analysis. Pestalospirane C (<b>3</b>) and stemphyspyrane (<b>4</b>) featured unprecedented spiroketal skeletons. In addition, the putative biosynthetic logic for compounds <b>1</b>-<b>4</b> was proposed. Antibacterial and cytotoxic activities of compounds <b>1</b>-<b>9</b> were evaluated. Stemphyspyrane (<b>4</b>) displayed promising antibacterial activity against different pathogens, especially against <i>Staphylococcus aureus, Porphyromonas gingivalis</i>, and methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) with MIC values of 3.125 μM, 6.25 μM, and 12.5 μM, respectively. It is promising as an antibacterial agent for further optimization.