Bioactive polyoxygenated cembranoids from a novel Hainan chemotype of the soft coral Sinularia flexibilis

Different chemotypes of Sinularia flexibilis exist in the Hainan island. Thus, a collection of this soft coral from a location different from the one of our previous study afforded three novel cembranoid esters featuring a n-butyl alcohol moiety, a structural element rare in natural products of both terrestrial and marine origin. The structures of the new compounds were elucidated by detailed spectroscopic analysis and by the comparison of their spectroscopic data with those reported in the literature. In addition, the absolute stereochemistry of the previously reported diepoxycembrene (9) was first time determined by the X-ray diffraction analysis. In bioassays, compounds 6-8 exhibited strong anti-inflammatory effect with IC50 values of 2.7, 4.7, and 4.2 mu M, respectively, whereas compound 5 displayed cytotoxicity against several cancer cells with IC50 values ranging from 8.9 to 27.4 mu M. A preliminary structural-activity relationship (SAR) was also described.