Versixanthones A–F, Cytotoxic Xanthone–Chromanone Dimers from the Marine-Derived Fungus Aspergillus versicolor HDN1009

Six unusual xanthone–chromanone dimers, versixanthones A–F (1–6), featuring different formal linkages of tetrahydroxanthone and 2,2-disubstituted chroman-4-one monomers, were isolated from a culture of the mangrove-derived fungus Aspergillus versicolor HDN1009. The absolute configurations of 1–6, representing the central and axial chirality elements or preferred helicities, were established by a combination of X-ray diffraction analysis, chemical conversions, and TDDFT-ECD calculations. The interconversion of different biaryl linkages between 1 and 4 and between 2 and 3 in DMSO by a retro-oxa-Michael mechanism provided insight into the formation of the xanthone–chromanone dimers and supported the assignments of their absolute configurations. Compounds 1–6 exhibited cytotoxicities against the seven tested cancer cell lines, with the best IC50 value of 0.7 μM. Compound 5 showed further inhibitory activity against topoisomerase I.