Penimeroandranoids A–D, DMOA-Derived Meroterpenoids from the Soil Fungus Penicillium sp. sb62 and Their Bioactivities

Four meroterpenoids derived from 3,5-dimethylorsellinic acid (DMOA), penimeroandranoids A-D (1-4), were isolated from the fermentation of the soil-derived fungus Penicillium sp. sb62. Their structures and absolute configurations were elucidated by HRESIMS, 1D and 2D NMR spectroscopic data, X-ray diffraction analysis, and quantum chemical calculations. Penimeroandranoid A (1) is characterized with a 6/6/6 tricyclic system with a unique 1-one-2-hydroxy-2-methyl-3-propanoatemethyl moiety. Penimeroandranoid B (2) constitutes the second 6/6/6 tricyclic meroterpenoid featuring a propyl residue. Penimeroandranoid C (3) represents the first example of a meroterpenoid harboring a 6/6/6/5 spirocyclic framework. Penimeroandranoid D (4) is a novel natural product sharing the core motif of asperterpene-type meroterpenoids but differing in the stereochemistry at C-5 and C-10. Biological evaluation revealed that compound 1 exhibits potent α-glucosidase inhibitory activity, while compounds 1-4 display notable anti-inflammatory and moderate immunosuppressive effects. Based on genomic analysis of Penicillium sp. sb62, plausible biosynthetic pathways for compounds 1-4 are proposed.