Terricoxanthones A-E, unprecedented dihydropyran-containing dimeric xanthones from the endophytic fungus Neurospora terricola HDF-Br-2 associated with the vulnerable conifer Pseudotsuga gaussenii

Abstract

An investigation on the secondary metabolites from a rice culture broth of the endophytic fungus Neurospora terricola HDF-Br-2 derived from the vulnerable conifer Pseudotsuga gaussenii led to the isolation and characterization of 34 structurally diverse polyketides (1-34). Seven of them are previously undescribed, including five unprecedented dihydropyran-containing (terricoxanthones A-E, 1-5, resp.) and one rare tetrahydrofuran-containing (terricoxanthone F, 6) dimeric xanthones. The structures were elucidated by spectroscopic methods and single-crystal X-ray diffraction analyses. Terricoxanthones each were obtained as a racemic mixture. Their plausible biosynthetic relationships were briefly proposed. Compounds 6, aspergillusone A (8), and alatinone (27) displayed considerable inhibition against Candida albicans with MIC values of 8-16 μg/mL. 4-Hydroxyvertixanthone (12) and 27 exhibited significant inhibitory activities against Staphylococcus aureus, with MIC values of 4-8 μg/mL. Furthermore, compounds 8 and 27 could disrupt biofilm of S. aureus and C. albicans at 128 μg/mL. The findings not only extend the skeletons of xanthone dimers and contribute to the diversity of metabolites of endophytes associated with the endangered Chinese conifer P. gaussenii, but could further reveal the important role of protecting plant species diversity in support of chemical diversity and potential sources of new therapeutics.

Keywords: (±)-terricoxanthones A–F; Antimicrobial; Dimeric xanthones; Endangered Chinese conifer; Neurospora terricola; Pinaceae; Pseudotsuga gaussenii; Sordariaceae.