New polyketides from dinoflagellate Amphidinium sp.

Abstract

Marine dinoflagellates have been recognized as a source of novel secondary metabolites with intriguing structures and interesting bioactivities [1]. In our continuing search for bioactive metabolites from Okinawan marine dinoflagellates, we have isolated a series of macrolides, amphidinolides, and long chain polyketides from cultured symbiotic marine dinoflagellates Amphidinium spp. [2]. Recently, we have investigated the culture medium of dinoflagellate Amphidinium sp., which was a symbiont of an acoel flatworm Amphiscolops sp., and isolated five new liner polyketides, amphidinins C˜G (1˜5), with known polyketides, amphidinin A (6) and amphidinolide Q (7) [3 – 5]. The analysis of spectral data revealed that 1˜4 were 4,5-seco-analogs of 7. The absolute configurations of 1˜4 have been elucidated by J-based configuration analysis (JBCA), modified Mosher's method, and chemical derivatization. Compounds 1˜4 corresponded to 4,5-secoamphidinolide Q, 4-O-α-D-ribofuranosyl-4,5-secoamphidinolide Q, 6,O-6-dihydro-4,5-secoamphidinolide Q, and 4-O-α-D-ribo-furanosyl-6,O-6-dihydro-4,5-secoamphidinolide Q, respectively. Compounds 2 and 4 were the first glycoside related to amphidinolides [6]. The structure of 5 was elucidated to be 9,12-O-seco-analog of 6 based on its spectral data. The absolute configuration of 5 has been elucidated to be 2R, 4R, 6S, 11R, and 12S by chemical shift comparison, JBCA, and modified Mosher's method [7]. The absolute configuration of 6 was also elucidated to be 2R, 4R, 6S, 9R, 11R, and 12S by JBCA, modified Mosher's method, and the density-functional theory calculations [8]. Compounds 1, 3, and 7 showed antimicrobial activities against some bacteria and fungi. Compounds 2 (IC50 16 µg/mL), 4 (IC50 32 µg/mL), and 5 (IC50 8 µg/mL) showed selective antifungal activity against Trichophyton mentagrophytes. Compound 6 showed antibacterial activity against Bacillus subtilis (MIC 16 µg/mL) and antifungal activity against Aspergillis niger (IC50 4 µg/mL).