Skeletal Diversity of Diterpenoids Isolated from the Soft Coral <i>Sclerophytum heterospiculatum</i> in Kikai Island

Five new compounds with diverse skeletons, namely, lobophytumins G (<b>1</b>, prenylgermacrane-type), H (<b>2</b>, spatane-type), sclerophytumins A (<b>3</b>, kikainane-type), B (<b>4</b>, prenyloplopanone-type), and <i>ent</i>-obscuronatin (<b>5</b>, prenylgermacrane-type), were isolated from the soft coral <i>Sclerophytum heterospiculatum</i> 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 <b>1</b>-<b>5</b> were determined through extensive spectroscopic data analysis, DFT-based DP4 analysis, and electronic circular dichroism (ECD) calculations. Notably, the <i>trans</i>-11-oxabicyclo[4.4.1]undecane skeleton observed in <b>3</b> 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 <b>4</b>. Based on the obtained relative and absolute configurations, biosynthetic pathways were also proposed. Furthermore, the cytotoxicities of isolated compounds <b>1</b>-<b>5</b> were evaluated against four human cancer cell lines.