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

Eight new terpenoids, including six alpha-methylene-delta-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.