Seco and Nor-seco Isodhilarane-Type Meroterpenoids from Penicillium purpurogenum and the Configuration Revisions of Related Compounds

Seco and nor-seco isodhilarane-type meroterpenoids (SIMs and NSIMs) are mainly found in Penicillium fungi and have been characterized by highly congested polycyclic skeletons and a broad range of bioactivities. However, the literature reports inconsistent configuration assignments for some SIMs and NSIMs, due to their complex polycyclic systems and multichiral centers. Herein, we described eight SIMs and NSIMs isolated from the EtOAc extract of Penicillium purpurogenum, which led to the configuration revisions of purpurogenolide C (1a), berkeleyacetal B (2a), chrysogenolide F (3a), and berkeleyacetal C (4a) as compounds 1-4, respectively. Furthermore, extensive re-evaluation of the experimental and computational C-13 NMR chemical shifts of the reported 39 SIMs and NSIMs provided an empirical approach for determining the C-9 relative configuration, according to the C-13 NMR chemical shifts of C-9, which contributed to the configuration revisions of another three SIMs (5a and 6a) and NSIMs (7a), denoted as compounds 5-7, respectively. Biological assays indicated that compound 3 exhibited cytotoxic activity against HepG2 and A549 cell lines with IC50 values of 5.58 and 6.80 mu M, respectively. Compounds 2-4, 8, 9, and 32 showed moderate hepatoprotective activity at 10 mu M in the APAP-induced HepG2 cell injury model.