Distachydrimanes A–F, phenylspirodrimane dimers and hybrids with cytotoxic activity from the coral-derived fungus Stachybotrys chartarum

By integrating one strain-many compounds (OSMAC) and LC–MS-based molecular networking strategies, distachydrimanes A–F (1–6), six novel phenylspirodrimane dimers and hybrids representing two types of unprecedented terpenoid-polyketide hybrid skeletons, were isolated from the modified fermented rice substrate of a coral-derived fungus Stachybotrys chartarum. All the structures incorporating their absolute configurations were elucidated based on comprehensive spectroscopic analyses, mainly including HRESIMS and NMR data, single-crystal X-ray diffraction (Cu Kα), and comparison of the experimental electronic circular dichroism (ECD) data. Architecturally, compounds 1–6 represent an unprecedented class of dimeric phenylspirodrimanes with an unexpected C-18–C-23′ linkage, of which compounds 1–3 also feature an unexpected 5-methyl-1,3-benzenediol moiety via a carbon-carbon linkage. The bioactivity assay demonstrated that compounds 1, 5 and 6 induced cell proliferation inhibition, G0/G1 cell cycle arrest, senescence and mitochondrial-mediated apoptosis in L1210 cells, highlighting their potentials as a new category of anticancer agents.