Sclerofish A and B: Two Pairs of Enantiomeric Diterpenoids Featuring a 4/7/6-Fused Tricyclic Scaffold from the Soft Coral Sclerophytum humesi

Two pairs of enantiomeric diterpenoids, (±)-sclerofish A (1) and (±)-sclerofish B (2), featuring a rare 4/7/6-fused tricyclic framework, were isolated from the soft coral Sclerophytum humesi by molecular networking-guided isolation. Their structures were elucidated by comprehensive spectroscopic analyses, including NMR, HRESIMS, TDDFT-ECD, and DP4+ analysis. A plausible biogenetic pathway, originating from geranylgeranyl pyrophosphate (GGPP) was proposed to rationalize the formation of the unusual bicyclo4.3.14,8decane subunit and the resulting 4/7/6-fused skeleton. Compound 1a/1b exhibited inhibition of Huh-7 cells with IC50 values of 5.1 ± 0.9 and 4.9 ± 0.3 μM, respectively, and showed selective cytotoxicity toward cancer cells (SI > 9.7), whereas compound 2a/2b displayed comparatively weaker activity. These findings expand the structural diversity of xeniaphyllane-type diterpenoids and highlight the soft coral S. humesi as a valuable source of structurally unique and biologically relevant marine natural products.