Structural diversity of terpenoids in the soft coral Sinularia flexibilis, evidenced by a collection from the South China Sea

Abstract

Eight new terpenoids, including six α-methylene-δ-lactone-bearing cembranoids (1–6), a 15-membered macrocyclic diterpenoid (7), and a biscembranoid (8), were isolated from South China Sea soft coral Sinularia flexibilis, along with five known analogues (9–13). Their structures including relative stereochemistry were elucidated by detailed spectroscopic analyses, chemical reactions and by comparison with literature data. Further, the structures of 8 and 10 were unambiguously confirmed by X-ray diffraction analyses. Compound 7, named epoxyflexibilene, represents the second 15-membered macrocyclic diterpenoid being discovered from marine sources, whereas sinulaflexiolide L (8) is the third member of the extremely rare cembrane dimers connected through C–C single bond. The discovery of these new isolates showed the high chemical diversity and ecological complexity of the animal S. flexibilis collected in different locations. In a bioassay, compound 9 exhibited potent anti-tumor activity targeting the inositol-requiring 1/X-box-binding protein 1 (IRE1/XBP1) signaling pathway.