Trisarcglaboids A and B, two cytotoxic lindenane sesquiterpenoid trimers with a unique polymerization mode isolated...

Trisarcglaboids A and B (1 and 2), representing the first example of lindenane sesquiterpenoid trimers repolymerized based on the classical [4 + 2] type dimer, together with known biogenic precursors chlorahololide D (3) and sarcandrolide A (4), were identified as chemical components of the root of Sarcandra glabra. The novel trimeric lindenane sesquiterpenoid skeletons, including their absolute configurations, were characterized using MS, NMR, ECD, and X-ray single crystal diffraction. The proposed Diels-Alder cycloaddition between Δ²⁽³⁾ of the tiglic acyl group of the classical [4 + 2] type dimer and Δ^15(4),5(6) of the third lindenane may serve as the key biogenic step. In addition, compound 1 exerted significant cytotoxicity against five human cancer cell lines with IC₅₀ values ranging from 1 to 7 μM, potentially through blocking Akt phosphorylation and activating the endogenous apoptosis pathway.