Euphohelides A-C, ent-Abietane-Type Norditerpene Lactones from Euphorbia helioscopia and Their Anti-Inflammatory Activities

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