Bioactive metabolites from marine organisms: the chemistry of Xestospongia Caycedoi, Diplosoma species Trididemnum solidum and the marine microbe Streptomyces species

Marine organisms continue to be an important source of novel natural products, often without structural precedent among terrestrial natural products. As part of continuing exploration of marine natural products, four projects are described involving three distinct phyla. To date, more than 40 novel metabolites have been isolated from sponges of the genus Xestospongia. Investigation of the chemistry of the Fijian sponge Xestospongia caycedoi resulted in the isolation of the isoquinoline quinone renierol along with the previously described mimosamycin. These metabolites are members of a large family of related compounds isolated from the genera Reniera and Xestospongia. Didemnid tunicates are an important source of novel bioactive marine natural products. Diplamine, isolated from the Fijian didemnid tunicate, Diplosoma sp., belongs to a large family of polycyclic aromatic alkaloid pigments. The structure of diplamine contains the most common tetracyclic backbone observed in these pigments. Diplamine is strongly cytotoxic towards L1210 murine leukemia cells in vitro with an IC50 of 0.02 mu-g/mL. The didemnins, depsipeptides isolated from the Caribbean tunicate Trididemnum solidum, are arguably the most important marine natural products isolated to date. Didemnin B is currently in phase II clinical trials as a potential chemotherapeutic agent against human tumors. A two-dimensional NMR study of didemnin B was undertaken which provided the complete NMR spectral assignments for this compound. The structure elucidation of nordidemnin B, a major constituent of Trididemnum solidum collected at Guadaloupe Island, in the eastern Caribbean, was also accomplished. Finally, the isolation and structure elucidation of the first peptides isolated from a marine bacterium are reported. CNB/091A and CNB/091B were isolated from Streptomyces sp. obtained from the skin of a jellyfish. The structure elucidation of these compounds relied heavily on 2D-NMR experiments including HMBC and TOCSY/ROESY experiments. The three-dimensional structure of CNB/091B was established by x-ray crystallography.