Diverse Chemosensitizing 8,9-Secolindenane-Type Sesquiterpenoid Oligomers and Monomers from Sarcandra glabra
Jun Chi1, Shanshan Wei1, Hongliang Gao1
1Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy , China Pharmaceutical University , Nanjing 210009 , P. R. China.
Abstract:
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.
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