Chamilactones A and B, Sesquiterpenes from the Endophytic Fungus Chaetomium nigricolor F5

A bioassay-guided chemical investigation of the endophytic fungus Chaetomium nigricolor F5 resulted in the discovery of two novel sesquiterpenes, chamilactones A and B (1 and 2), with a new 9,10-seco-15-nor-isoilludalane carbon skeleton, together with several biosynthetically related precursors (3-8). Their structures and absolute configurations were elucidated by the analysis of MS, NMR, calculated 13C chemical shifts, ECD calculations, and single-crystal X-ray diffraction data. It was proposed that an unprecedented carbon-carbon bond cleavage between C-9 and C-10 in 3-8 was the key step in the biosynthetic pathway of 1 and 2. Compound 3 displayed potent neuroprotective effects by reducing the phosphorylation level of p65 and inhibiting its nuclear translocation in the TLR4-mediated NF-κB signaling pathway in LPS-induced BV2 microglial cells.