Discovery of Cymopolyphenols A-F From a Marine Mesophotic Zone Sponge-Associated Fungus sp. NBUF082.

Mesophotic coral ecosystems (MCEs) have complex but understudied biodiversity, especially for natural products discovery. Untargeted metabolomics research on 80 extracts prepared from marine sponge-associated fungi, half from shallow reefs (<30 m) and half from MCEs (30-150 m), facilitated prioritization for further study a fungus from a 103 m deep sponge. LC-MS target-directed isolation yielded a series of new compounds, cymopolyphenols A-F (-), and two known phenylspirodrimanes, F1839-I () and stachybotrylactone (). This is the first report of natural products from the recently described genus, . Compounds - and contain a dihydroisobenzofuran moiety, and - are low-order polymers of with novel scaffolds. The structures of the compounds were established by spectroscopic and spectrometric data interpretation, with further support from X-ray crystallography studies of and . Compound undergoes facile racemization in solution and was found to crystalize as a racemic mixture. Compound was also obtained in racemic form, and after chiral chromatography, both separated enantiomers racemized in solution by a presumed keto-enol tautomerization. Compounds and - were found to be weakly antimicrobial (MIC 16-64 μg/ml) against several Gram-positive and Gram-negative human or aquatic pathogens, compound was shown to chelate iron at 10 μM, and activated plant disease resistance in a transgenic model organism.