Discovery of Three Macrocyclic Diterpenoid Skeletons from Croton laevigatus and Their NF-κB Inhibitory Activity.

Phytochemical investigation of Croton laevigatus yielded six macrocyclic diterpenoids, craeviganoids A-F (1-6), featuring three novel carbon skeletons: two distinct types of 13-membered diterpenoid lactones (1-3) bearing a rare bridgehead alkene, and a 14-membered furanoditerpenoid skeleton (4-6). Their structures were elucidated by spectroscopic analysis, X-ray crystallography, and quantum chemical calculations, revealing distinct solid-state and solution conformations for 1. Moreover, compound 4 potently inhibited NF-κB and exhibited anti-inflammatory activity.