Astellolides R–W, Drimane-Type Sesquiterpenoids from an <i>Aspergillus parasiticus</i> Strain Associated with an Isopod

Abstract

Sesquiterpenoids with a cage-like multiring frame are rarely found in nature. Mining of the isopod-derived fungus <i>Aspergillus parasiticus</i> SDU001 by the one strain-many compounds (OSMAC) strategy unexpectedly led to the discovery of fungal drimane-type sesquiterpenoids astellolide R (<b>1</b>), featuring an unusual cage-like 6/6/5/6/5 pentacyclic ring system, astellolide S (<b>2</b>), possessing a rare nicotinic acid building block, and astellolides T-W (<b>3</b>-<b>6</b>). Their structures were comprehensively assigned by spectroscopic data analysis, single-crystal X-ray diffraction, and electronic circular dichroism calculations. Furthermore, compounds <b>3</b> and <b>5</b> exhibited anti-inflammatory activity by inhibiting the lipopolyssacharide-induced NO production in RAW264.7 macrophages with IC₅₀ values of 6.1 ± 0.8 and 6.8 ± 0.8 μM, respectively. A putative biosynthetic pathway for <b>1</b> is proposed. Our results enlarge the chemical space of the drimane-type sesquiterpenoids generated from endophytic fungi.