Uncommon Diterpenoids from the South China Sea Soft Coral and Their Stereochemistry.

The chemical investigation of the South China Sea soft coral has resulted in the isolation of a library of diverse diterpenoids, including four new cembranoids, namely, humilisins A-D (-), two new uncommon diterpenoids possessing a tetradecahydrocyclopenta[3',4']cyclobuta[1',2':4,5]cyclonona[1,2-]oxirene ring system, namely, humilisins E and F ( and ), and eight known related compounds (-). Humilisin A () is the first cembranoid with an ether linkage between C-3 and C-7. The structures and absolute configurations of - were determined by extensive spectroscopic data analyses, chemical reactions, and a series of quantum chemical calculations including quantum mechanical-nuclear magnetic resonance (QM-NMR), time-dependent density functional theory-electronic circular dichroism (TDDFT-ECD), and optical rotatory dispersion (ORD) methods. In bioassay, compound displayed anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated BV-2 microglia cells.