Euphohelides A–C, <i>ent</i>-Abietane-Type Norditerpene Lactones from <i>Euphorbia helioscopia</i> and Their Anti-Inflammatory Activities

Abstract

Three unreported <i>ent</i>-abietane-type norditerpene lactones, euphohelides A-C (<b>1</b>-<b>3</b>), and 11 known analogs (<b>4</b>-<b>14</b>) were isolated from the whole plants of <i>Euphorbia helioscopia</i> L. Euphohelide A (<b>1</b>) is an unprecedented 2-<i>nor</i>-<i>ent</i>-abietane lactone bearing a unique 5/6/6/5 tetracyclic system. Euphohelides B (<b>2</b>) and C (<b>3</b>) possess 2-<i>nor</i>-6/6/6/5 and 2,3-<i>dinor</i>-5/6/6/5 dilactone tetracyclic moieties, respectively. Their structures were established by spectroscopic methods, computational ECD, and X-ray crystallographic analyses. A biomimetic synthesis of <b>1</b> was achieved from precursor <b>4</b> based on the speculative biogenetic pathway. Compounds <b>1</b> and <b>5</b> significantly alleviated the release of LPS-induced NO with IC₅₀ values of 32.98 ± 1.13 and 33.82 ± 3.25 μM, which might be related to the regulation of the NF-κB signaling pathway.