Chlorahupetenes A–D, Four Eudesmane-Type Sesquiterpenoid Dimer Enantiomers with Two Unusual Carbon Skeletons from <i>Chloranthus henryi</i> Var. <i>hupehensis</i>

Abstract

(+)- and (-)-Chlorahupetenes A (<b>1a</b> and <b>1b</b>), B (<b>2a</b> and <b>2b</b>), C (<b>3a</b> and <b>3b</b>), and D (<b>4a</b> and <b>4b</b>), four unique enantiomeric pairs of eudesmane-type sesquiterpenoid dimers with two new carbon skeletons, were isolated from the aerial parts of <i>Chloranthus henryi</i> var. <i>hupehensis</i>. Compounds <b>1</b> and <b>2</b> possess an unprecedented 6/6/5/6/6 pentacyclic carbon skeleton with a new dimerization pattern of two eudesmane-type sesquiterpenoids. Compounds <b>3</b> and <b>4</b>, which are fused with two eudesmane-type sesquiterpenoids via an unprecedented five-membered <i>O</i>-heterocyclic ring, represent a new 6/6/5/5/6/6/5 heptacyclic ring system. The structures of the compounds were determined through spectroscopic data and X-ray crystallography. Compounds <b>1a</b>-<b>3b</b> significantly inhibited NO production with IC₅₀ values ranging from 9.62 to 12.91 μM. Moreover, compounds <b>1b</b> and <b>3a</b> suppressed the production of a proinflammatory mediator (TNF-α) and enzyme expression (iNOS) at the mRNA level.