Diverse Chemosensitizing 8,9-Secolindenane-Type Sesquiterpenoid Oligomers and Monomers from Sarcandra glabra

The theoretical analysis and biomimetic conversion confirmed that the oxidative cleavage of the Δ8,9 double bond of chloranthalactone A (I), an abundant lindenane-type sesquiterpenoid in Chloranthaceae plants, generates 8,9-secolindenane (II) with active aldehyde and maleic anhydride fragments that can capture other fragments and produce oligomeric molecules. A careful phytochemical investigation of the leaves of Sarcandra glabra led to the discovery of eight novel 8,9-secolindenane-type sesquiterpenoid oligomers (sarglalactones A–H, compounds 1–8), including three unprecedented trimers (1–3), five unusual dimers (4–8), and five 8,9-secolindenane monomers (sarglalactones I–M, 9–13). Their structures were determined by comprehensive HRMS, NMR, circular dichroism, and X-ray diffraction analyses. Bioassay results showed that these oligomers significantly reversed the multidrug resistance of MCF-7/doxorubicin (DOX) cells and increased the sensitivity of U2 OS cells to DOX by downregulating the HMGB1 expression.