BREVISULCATIC ACIDS FROM A MARINE MICROALGAL SPECIES IMPLICATED IN A TOXIC EVENT IN NEW ZEALAND

Ladder-frame polyethers, known as brevisulcatic acids (BSXs)-1 (1), -2 (2),-4 (3),-5 (4) and-7 (5), were isolated from the dinoflagellate Karenia brevisulcata as potential causative toxins of a harmful algal event in New Zealand in 1998. The structures of 2, 4, and 5 were elucidated in this study. Brevisulcatic acids possessed a common fused nine ether-ring backbone, with a size and sequence determined to be 8/6/8/9/7/7/6/6/6. Rings B, C, H, I and J of the brevisulcatic acids were similar to those of brevetoxin A, a well-known polyether toxin. BSX-5 (4) had a gamma-lactone as the 5-membered A-ring, analogous to brevetoxin A, while in BSX-2 (2) and BSX-7 (5) the lactone was present in its seco-acid form. In addition to this backbone variation, there were also some structural difference in side-chain substituents, with 2 and 4 having a 2-methylenepropionic acid unit, and 5 a 2-methylenepropanol unit. Cytotoxicity of 4 against neuroblastoma cells indicated that not only the structures but also activity of brevisulcatic acids are similar to those of brevetoxin A. This indicates that brevisulcatic acids potentially played a significant role in the toxicity observed during the only documented Karenia brevisulcata bloom to date.