The chemical investigation of the South China Sea soft coral Sinularia humilis has resulted in the isolation of a library of diverse diterpenoids, including four new cembranoids, namely, humilisins A−D (1−4), two new uncommon diterpenoids possessing a tetradecahydrocyclopenta[3′,4′]cyclobuta[1′,2′:4,5]cyclonona[1,2-b]oxirene ring system, namely, humilisins E and F (5 and 6), and eight known related compounds (7−14). Humilisin A (1) is the first cembranoid with an ether linkage between C-3 and C-7. The structures and absolute configurations of 1−8 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 6 displayed anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated BV-2 microglia cells.

A novel diterpenoid, sinunanolobatone A (1), featuring an unprecedented bicyclo[13.1.0]pentadecane carbon framework, along with two new casbane diterpenoids (2 and 3), and five known related ones (4-8) were isolated from the Sanya soft coral Sinularia nanolobata. The structures of the new compounds were established by detailed spectroscopic analysis, X-ray diffraction analysis, chemical reactions, or quantum chemical computation method. A plausible biosynthetic pathway of 1 and its biogenetic relationship with co-occurring casbanes was proposed. In bioassay, the novel compound 1 showed significant inhibitory activity against lipopolysaccharide (LPS) induced inflammation in BV-2 microglial cells.