Nine sesquiterpenoid dimers with four unprecedented types of carbon skeleton from Chloranthus henryi var. hupehensis

Abstract

Chlorahupetones A–I (1–9), nine sesquiterpenoid dimers, were isolated from Chloranthus henryi var. hupehensis. Their structures were characterized by nuclear magnetic resonance (NMR), electronic circular dichroism (ECD), and X-ray diffraction analysis. Compound 1 features a unique 3/5/6/5/4/7/7/5-fused octacyclic carbon skeleton of lindenane-type and guaiane-type sesquiterpenoid monomers bridged by a seven-four-five-membered ring system. Compounds 2 and 3, possessing an unusual 3/5/6/5/4/7/6/5-fused carbon skeleton, are two structural analogues of 1. Compounds 4 and 5 possess an unprecedented 3/5/6/6/4/6/6/3/5-fused carbon framework. Compound 6 is a unique C₂-symmetric cyclic rearranged lindenane-type sesquiterpenoid dimer. Compounds 7–9 are lindenane-type sesquiterpenoid dimers featuring a carbon framework via the formation of a C-11–C-7′ bond with an aromatized ring D and a five-membered lactone ring fused at C-11 and C-7′. Compounds 1, 7, 8, and 9 were found to show significant cytotoxicities against human non-small-cell lung cancer (NSCLC) A549 cells, human glioma U87 cells, and hepatocellular carcinoma SMMC-7721 cells. Compound 7 exhibited the most potent cytotoxicity against A549 cells with an IC₅₀ value of 0.43 ± 0.12 μM, even about 4 times than paclitaxel (IC₅₀ = 1.62 ± 0.13 μM). Moreover, compound 7 showed significant efficacy in inducing cell cycle arrest at the G0/G1 phase and apoptosis in A549 cells.