Brevisulcenal-F: A Polycyclic Ether Toxin Associated with Massive Fish-kills in New Zealand

A novel marine toxin, brevisulcenal-F (KBT-F, from karenia brevisulcata toxin) was isolated from the dinoflagellate <i>Karenia brevisulcata</i>. A red tide of <i>K. brevisulcata</i> in Wellington Harbour, New Zealand, in 1998 was extremely toxic to fish and marine invertebrates and also caused respiratory distress in harbor bystanders. An extract of <i>K. brevisulcata</i> showed potent mouse lethality and cytotoxicity, and laboratory cultures of <i>K. brevisulcata</i> produced a range of novel lipid-soluble toxins. A lipid soluble toxin, KBT-F, was isolated from bulk cultures by using various column chromatographies. Chemical investigations showed that KBT-F has the molecular formula C₁₀₇H₁₆₀O₃₈ and a complex polycyclic ether nature. NMR and MS/MS analyses revealed the complete structure for KBT-F, which is characterized by a ladder-frame polyether scaffold, a 2-methylbut-2-enal terminus, and an unusual substituted dihydrofuran at the other terminus. The main section of the molecule has 17 contiguous 6- and 7-membered ether rings. The LD₅₀ (mouse i.p.) for KBT-F was 0.032 mg/kg.