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 crystallographic 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 IC 50 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.