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

Sesquiterpenoids with a cage-like multiring frame arerarely foundin nature. Mining of the isopod-derived fungus Aspergillusparasiticus SDU001 by the one strain-many compounds(OSMAC) strategy unexpectedly led to the discovery of fungal drimane-typesesquiterpenoids astellolide R (1), featuring an unusualcage-like 6/6/5/6/5 pentacyclic ring system, astellolide S (2), possessing a rare nicotinic acid building block, and astellolidesT-W (3-6). Their structureswere comprehensively assigned by spectroscopic data analysis, single-crystalX-ray diffraction, and electronic circular dichroism calculations.Furthermore, compounds 3 and 5 exhibitedanti-inflammatory activity by inhibiting the lipopolyssacharide-inducedNO production in RAW264.7 macrophages with IC50 valuesof 6.1 & PLUSMN; 0.8 and 6.8 & PLUSMN; 0.8 & mu;M, respectively. A putativebiosynthetic pathway for 1 is proposed. Our results enlargethe chemical space of the drimane-type sesquiterpenoids generatedfrom endophytic fungi.