Caribenolide revisited. Reisolation of caribenolide-I together with new congeners

Caribenolide-I [1] was originally discovered from the cell extract of a free-swimming Caribbean dinoflagellate Amphidinium gibbosum by Shimizu and coworkers. The structure was interpreted to be a 26-membered macrolide containing a 6-membered hemiacetal ring, a tetrahydrofuran ring, an epoxide, a ketone carbonyl, four C₁ branches, and five hydroxyl groups. On the other hand, Kobayashi et al. reported the isolation of amphidinolide N [2] isolated from a symbiotic dinoflagellate Amphidinium species earlier than the report of caribenolide-I. The structure of amphidinolide N was elucidated to be the ring-opening form at the C-21-C-24 tetrahydrofuran ring for caribenolide-I.

Caribenolide-I was reported to exhibit strong cytotoxic activity against tumor cell lines and in vivo antitumor activity. Amphidinolide N also showed extremely potent cytotoxic activity. Caribenolide-I as well as amphidinolide N would therefore also appear to be a promising anticancer therapeutic lead. Nevertheless, the scarcity of materials has prevented more detailed studies. Because stereochemistries of caribeolide-I and amphidinolide N have not 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 together a three new caribenolide-I congeners from two benthic Amphidinium strains collected off Iriomote Island, Japan. In this symposium, we will discuss the isolation of these four compounds, structural relationship between caribenolide-I and amphidinolide N, and structure elucidation of three new compounds.

References: 1. Bauer I, Maranda Y, Young K A, Shimizu Y, Fairchild C, Cornell L, MacBeth J, Huang S (1995)J Org Chem 60: 1084–1086.

2. Ishibashi M, Yamaguchi N, Sasaki T, Kobayashi J (1994)J Chem Soc, Chem Commun,1445–1446.