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

Four meroterpenoids derived from 3,5-dimethylorsellinic acid (DMOA), penimeroandranoids A-D (<b>1</b>-<b>4</b>), were isolated from the fermentation of the soil-derived fungus <i>Penicillium</i> 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 (<b>1</b>) is characterized with a 6/6/6 tricyclic system with a unique 1-one-2-hydroxy-2-methyl-3-propanoatemethyl moiety. Penimeroandranoid B (<b>2</b>) constitutes the second 6/6/6 tricyclic meroterpenoid featuring a propyl residue. Penimeroandranoid C (<b>3</b>) represents the first example of a meroterpenoid harboring a 6/6/6/5 spirocyclic framework. Penimeroandranoid D (<b>4</b>) 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 <b>1</b> exhibits potent α-glucosidase inhibitory activity, while compounds <b>1</b>-<b>4</b> display notable anti-inflammatory and moderate immunosuppressive effects. Based on genomic analysis of <i>Penicillium</i> sp. sb62, plausible biosynthetic pathways for compounds <b>1</b>-<b>4</b> are proposed.