Isolation and Absolute Configurations of Diversiform C17, C21 and C25 Terpenoids from the Marine Sponge Cacospongia sp.

Chemical investigation of MeOH extract of a South China Sea sponge Cacospongia sp. yielded 15 terpenoids belonging to three different skeleton-types, including the unusual C17 γ-lactone norditerpenoids (1⁻3), the rare C21 pyridine meroterpenoid (7), and the notable C25 manoalide-type sesterterpenoids (4⁻6, 8⁻10). Compounds 1⁻5 were initially obtained as enantiomers, and were further separated to be optically pure compounds (1a, 1b, 2a, 2b, 3a-r, 3b-r, 4a, 4b, 5a and 5b) by chiral HPLC, with a LiAlH₄ reduction aid for 3. Compounds 3a/3b (a pair of inseparable enantiomers), 4a, 5a, 6, and 7 were identified as new compounds, while 1a/1b and 2a/2b were obtained from a natural source and were determined for their absolute configurations for the first time. This is also the first time to encounter enantiomers of the well-known manoalide-type sesterterpenoids from nature. The structures with absolute configurations of the new compounds were unambiguously determined by comprehensive methods including HR-ESI-MS and NMR data analysis, optical rotation comparison, experimental and calculated electronic circular dichroism (ECD), and Mo₂(OAc)₄ induced circular dichroism (ICD) methods. The cytotoxicity of the isolates against selected human tumor cell lines was evaluated, however, the tested compounds showed no activity against selected cell lines.