Facile constructed meroterpenoids with novel hexadecahydroacephenanthrylene carbon skeleton using the biotransformation and chemical synthesis method.

Bioaspermeroterpenoid A (1), the first meroterpenoid with an unprecedented hexadecahydroacephenanthrylene carbon skeleton, together with two analogues bioaspermeroterpenoids B and C (2 and 3) were co-isolated from the biotransformation extract of aspermeroterpene C by the fungus Penicillium herquei GZU-31-6. On the other hand, bioaspermeroterpenoid Aa (1a) featuring the same hexadecahydroacephenanthrylene carbon skeleton was synthesized from the precursor aspermeroterpene C by the nucleophilic addition reaction in the presence of CHONa. Furthermore, bioaspermeroterpenoids A and C showed good inhibitory activities against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 cells with IC values of 26.08 and 7.50 µM, respectively, compared to the positive control (Indomethacin, IC 24.1 µM). Especially, bioaspermeroterpenoids A and C also significantly suppressed the protein expression of iNOS and COX-2 at the concentration of 12.5 μM.