The theoretical analysis and biomimetic conversion confirmed that the oxidative cleavage of the Δ 8,9 double bond of chloranthalactone A (I), an abundant lindenane-type sesquiterpenoid in Chloranthaceae plants, generates 8,9secolindenane (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.
Detailed isolation procedures, biological activity experiments, and full spectroscopic spectra (MS, UV, IR, 1D and 2D NMR, and ECD) for compounds 1 and 2 (PDF)Accession Codes CCDC 1880242 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk
Sarcandra glabra | Molecular networks | Natural products | Structural elucidation | Peroxides Sarcaglarols AD (1-4), two pairs of lindenane−monoterpene heterodimers fused by a 1,2-dioxane moiety, were discovered and isolated from the leaves of Sarcandra glabra guided by MS/MS molecular networking-based strategy. Their planar structures, absolute configurations of basic skeleton and flexible polyhydric side chain were established by analysis of HRESIMS, NMR spectroscopic data, ECD spectrum, and the X-ray diffraction study of isopropylidene derivatives. An intermolecular [2+2+2] cycloaddition may play a key role in the biosynthesis pathway of the 1,2-dioxane moiety fused lindenane−monoterpene heterodimer skeleton, which can be recognized as the biogenetic precursors of our previous reported lindenane−normonoterpene conjugates. In addition, compounds 1, 3 and 4 exhibited moderate inhibitory effects of lipid accumulation in free fatty acid-exposed L02 cells.
Sarglaromatics A−E (1−5, respectively), five unprecedented naphthalene-like architecture-fused norlindenane sesquiterpene dimers, were discovered from the roots of Sarcandra glabra. The unique naphthalene core skeleton was obtained from classical lindenane [4 + 2] dimers via a free-radical-mediated C11− C11′ bond formation reaction and 12'-decarboxylation. The highly fused octonary ring skeleton was elucidated by HRMS, NMR, ECD, quantum chemical calculations, and biogenetic inspiration. Compounds 1 and 2 showed significant anti-nonalcoholic steatohepatitis (NASH) activity by inhibiting lipid deposition in L02 cells.
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