Diverse Chemosensitizing 8,9-Secolindenane-Type Sesquiterpenoid Oligomers and Monomers from <i>Sarcandra glabra</i>

Abstract

The theoretical analysis and biomimetic conversion confirmed that the oxidative cleavage of the Δ^8,9 double bond of chloranthalactone A (<b>I</b>), an abundant lindenane-type sesquiterpenoid in Chloranthaceae plants, generates 8,9-secolindenane (<b>II</b>) with active aldehyde and maleic anhydride fragments that can capture other fragments and produce oligomeric molecules. A careful phytochemical investigation of the leaves of <i>Sarcandra glabra</i> led to the discovery of eight novel 8,9-secolindenane-type sesquiterpenoid oligomers (sarglalactones A-H, compounds <b>1-8</b>), including three unprecedented trimers (<b>1</b>-<b>3</b>), five unusual dimers (<b>4-8</b>), and five 8,9-secolindenane monomers (sarglalactones I-M, <b>9-13</b>). 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.