抄録
Marine dinoflagellates of the genus Amphidinium are well-known as a producer of unique cytotoxic metabolites. Kobayashi et al. reported the isolation of amphidinolide N^3 (1) from a symbiotic dinoflagellate Amphidinium species in 1994. The structure was interpreted to be a 26-membered macrolide containing a 6-membered hemiacetal ring, an epoxide, a ketone carbonyl, four C1 branches, and seven hydroxyl groups. On the other hand, caribenolide-I4 (2) was discovered from the cell extract of a free-swimming Caribbean dinoflagellate Amphidinium gibbosum by Shimizu and coworkers. The structure of caribenolide-I (2) was elucidated to be THE form at the C-21-C-24 instead of the diol moiety for 1. Caribenolide-I (2) was reported to exhibit strong cytotoxic activity against tumor cell lines and in vivo antitumor activity. Amphidinolide N (1) also showed extremely potent cytotoxic activity. Amphidinolide N (1) as well as caribenolide-I (2) would therefore also appear to be promising anticancer therapeutic leads. Nevertheless, the scarcity of materials has prevented more detailed studies. Because stereostructures of 1 and 2 have not been determined yet, it is difficult to supply the sample by synthesis. In our investigation for anticancer drug leads from the Amphidinium dinoflagellates, we have isolated caribenolide-I (2) together a two new caribenolide-I congeners (3 and 4) from two benthic Amphidinium strains collected off Iriomote Island, Japan. In this symposium, we will discuss the isolation and structure elucidation of these three compounds and structural relationship between amphidinolide N (1) and caribenolide-I (2).
