Skeletal Diversity of Diterpenoids Isolated from the Soft Coral Sclerophytum heterospiculatum in Kikai Island

Five new compounds with diverse skeletons, namely, lobophytumins G (1, prenylgermacrane-type), H (2, spatane-type), sclerophytumins A (3, kikainane-type), B (4, prenyloplopanone-type), and ent-obscuronatin (5, prenylgermacrane-type), were isolated from the soft coral Sclerophytum heterospiculatum collected from Kikai Island, Kagoshima Prefecture, Japan. Their chemical structures, including their relative configurations, were elucidated by detailed analysis of spectroscopic data such as NMR and direct analysis in real-time time-of-flight mass spectrometry (DART-TOF MS), as well as by comparison with related known compounds. The relative and absolute configurations of the cyclic skeletons in 1–5 were determined through extensive spectroscopic data analysis, DFT-based DP4 analysis, and electronic circular dichroism (ECD) calculations. Notably, the trans-11-oxabicyclo­[4.4.1]­undecane skeleton observed in 3 represents the first report of this framework from a marine organism. In addition, DP4 analysis distinguished the asymmetric center at C-11 in the acyclic portion, thereby revealing the stereochemistry of the linear side chain bearing a terminal C5 prenyl unit in 4. Based on the obtained relative and absolute configurations, biosynthetic pathways were also proposed. Furthermore, the cytotoxicities of isolated compounds 1–5 were evaluated against four human cancer cell lines.