Anti-inflammatory butenolide derivatives from the coral-derived fungus Aspergillus terreus and structure revisions of aspernolides D and G, butyrolactone VI and 4,8-diacetoxy butyrolactone VI

Chemical investigation of the coral-derived fungus Aspergillus terreus led to the discovery of ten butenolide derivatives (1-10), including four new ones (1-4). The new structures were characterized on the basis of comprehensive spectroscopic analysis, including 1D and 2D NMR and HRESIMS data. Compounds 1 and 2 were a pair of rare C-8 epimers with vicinal diol motifs. The absolute configurations of 1-4 were determined via [Mo-2(AcO)(4)] induced circular dichroism (ICD) spectra and comparison of their experimental ECD spectra. Importantly, the structures of reported aspernolides D and G, butyrolactone VI and 4,8-diacetoxy butyrolactone VI have been correspondingly revised via a combined strategy of experimental validations, C-13 NMR predictions by ACD/Labs software, and C-13 NMR calculations. Herein we provide valuable referenced C-13 NMR data (C-7, C-8, and C-9) for the structure elucidations of butenolide derivatives with 1-(2-hydroxyphenyl)-3-methylbutane-2,3-diol, 2-(2,3-dihydrobenzofuran-2-yl)propan-2-ol, or 2,2-dimethylchroman-3-ol motifs. Additionally, all the isolates (1-10) were assessed for anti-inflammatory activity by measuring the amount of NO production in lipopolysaccharide (LPS)-induced RAW 264.7 mouse macrophages, and compound 10 showed an even stronger inhibitory effect than the postive control indomethacin, presenting it as a promising lead compound for the development of new anti-inflammatory agents.