Diketopiperazine and Diphenylether Derivatives from Marine Algae-Derived OUCMDZ-2738 by Epigenetic Activation.

A chemical-epigenetic method was used to enhance the chemodiversity of a marine algicolous fungus. Apart from thirteen known compounds, (+)-brevianamide R ((+)-), (‒)-brevianamide R ((‒)-), (+)-brevianamide Q ((+)-), (‒)-brevianamide Q ((‒)-), brevianamide V ((+)-), brevianamide W ((‒)-), brevianamide K (), diorcinol B (), diorcinol C (), diorcinol E (), diorcinol J (), diorcinol (), 4-methoxycarbonyldiorcinol (), two new compounds, (+)- and (‒)-brevianamide X ((+)- and (‒)- )), as well as a new naturally occurring one, 3-[6-(2-methylpropyl)-2-oxo-1-pyrazin-3-yl]propanamide (), were isolated from chemical-epigenetic cultures of OUCMDZ-2738 with 10 µM vorinostat (SAHA). Compared to cultures in the same medium without SAHA, compounds ⁻, , , , and were solely observed under SAHA condition. The structures of these compounds were elucidated based on spectroscopic analysis, specific rotation analysis, ECD, and X-ray crystallographic analysis. (±)-, (±)-, and (±)- were further resolved into the corresponding optically pure enantiomers and their absolute configurations were determined for the first time. Compounds and showed selective antibacterial against with a minimum inhibitory concentration (MIC) of 17.4 and 13.9 μM, respectively. Compound exhibited better α-glucosidase inhibitory activity than the assay control acarbose with IC values of 117.3 and 255.3 μM, respectively.