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

Abstract

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-1H-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 IC50 values of 117.3 and 255.3 μM, respectively.

Bioactive Indolyl Diketopiperazines from the Marine Derived Endophytic Aspergillus versicolor DY180635

“…Furthermore, the same ECD cotton effects ( Figure 3 C) of 2 compared to 1 indicated that the absolute configuration of C-9 in 2 was consistent with that in 1 . This result suggested that within the used spectral window, the ECD cotton effects were mainly caused by the chiral center of C-9 in both compounds 1 and 2 , and it could also be confirmed by the experimental ECD data of (+)-brevianamide V and (−)-brevianamide V [ 35 ]. Thus, the absolute configuration of compound 2 was ascertained as (6 S ,9 S ).…”

New Diketopiperazines from a Marine-Derived Fungus Strain Aspergillus versicolor MF180151

“…Brevianamides belong to a class of naturally occurring 2,5-diketopiperazine alkaloids, which are mainly produced by fungi of Penicillium and Aspergillus [6,9,32,35,36]. In this research, three pairs of new brevianamides ((±)- 1 –(±)- 3 ) were isolated and their relative configurations were elucidated according to the 1D, 2D NMR, HRESIMS, UV.…”

Chemical diversity and biological function of indolediketopiperazines from marine-derived fungi

“…In 2019, a pair of enantiomers, (+)-and (−)-brevianamide X (95 and 96), was isolated from chemical-epigenetic cultures of A. versicolor OUCMDZ-2738 with 10 μmol/L fluinostat (SAHA). Compared to cultures in the same medium without SAHA, these two compounds were solely observed under SAHA condition (Liu et al 2019).…”