Diketopiperazine and Diphenylether Derivatives from Marine Algae-Derived Aspergillus versicolor 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 ((+)- 3 ), (‒)-brevianamide R ((‒)- 3 ), (+)-brevianamide Q ((+)- 4 ), (‒)-brevianamide Q ((‒)- 4 ), brevianamide V ((+)- 5 ), brevianamide W ((‒)- 5 ), brevianamide K ( 6 ), diorcinol B ( 7 ), diorcinol C ( 8 ), diorcinol E ( 9 ), diorcinol J ( 10 ), diorcinol ( 11 ), 4-methoxycarbonyldiorcinol ( 12 ), two new compounds, (+)- and (‒)-brevianamide X ((+)- and (‒)- 2 )), as well as a new naturally occurring one, 3-[6-(2-methylpropyl)-2-oxo-1 H -pyrazin-3-yl]propanamide ( 1 ), were isolated from chemical-epigenetic cultures of Aspergillus versicolor OUCMDZ-2738 with 10 µM vorinostat (SAHA). Compared to cultures in the same medium without SAHA, compounds 1 ⁻ 4 , 8 , 9 , 11 , and 12 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. (±)- 3 , (±)- 4 , and (±)- 5 were further resolved into the corresponding optically pure enantiomers and their absolute configurations were determined for the first time. Compounds 11 and 12 showed selective antibacterial against Pseudomonas aeruginosa with a minimum inhibitory concentration (MIC) of 17.4 and 13.9 μM, respectively. Compound 10 exhibited better α-glucosidase inhibitory activity than the assay control acarbose with IC ₅₀ values of 117.3 and 255.3 μM, respectively.