Astellolides R-W, Drimane-Type Sesquiterpenoids from an Aspergillus parasiticus Strain Associated with an Isopod.

ABSTRACT

Sesquiterpenoids with a cage-like multiring frame are rarely found in nature. Mining of the isopod-derived fungus Aspergillus parasiticus SDU001 by the one strain-many compounds (OSMAC) strategy unexpectedly led to the discovery of fungal drimane-type sesquiterpenoids astellolide R (1), featuring an unusual cage-like 6/6/5/6/5 pentacyclic ring system, astellolide S (2), possessing a rare nicotinic acid building block, and astellolides T-W (3-6). Their structures were comprehensively assigned by spectroscopic data analysis, single-crystal X-ray diffraction, and electronic circular dichroism calculations. Furthermore, compounds 3 and 5 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 1 is proposed. Our results enlarge the chemical space of the drimane-type sesquiterpenoids generated from endophytic fungi.