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

Abstract

Chemical investigation of MeOH extract of a South China Sea sponge <i>Cacospongia</i> sp. yielded 15 terpenoids belonging to three different skeleton-types, including the unusual C₁₇ <i>γ</i>-lactone norditerpenoids (<b>1</b>⁻<b>3</b>), the rare C₂₁ pyridine meroterpenoid (<b>7</b>), and the notable C₂₅ manoalide-type sesterterpenoids (<b>4</b>⁻<b>6</b>, <b>8</b>⁻<b>10</b>). Compounds <b>1</b>⁻<b>5</b> were initially obtained as enantiomers, and were further separated to be optically pure compounds (<b>1a</b>, <b>1b</b>, <b>2a</b>, <b>2b</b>, <b>3a-r</b>, <b>3b-r</b>, <b>4a</b>, <b>4b</b>, <b>5a</b> and <b>5b</b>) by chiral HPLC, with a LiAlH₄ reduction aid for <b>3</b>. Compounds <b>3a</b>/<b>3b</b> (a pair of inseparable enantiomers), <b>4a</b>, <b>5a</b>, <b>6</b>, and <b>7</b> were identified as new compounds, while <b>1a</b>/<b>1b</b> and <b>2a</b>/<b>2b</b> 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.