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

• Published in: Journal of the American Chemical Society 2012-03, Vol.134 (10), p.4963-4968
• Main Authors: Hamamoto, Yuka, Tachibana, Kazuo, Holland, Patrick T, Shi, Feng, Beuzenberg, Veronica, Itoh, Yoshiyuki, Satake, Masayuki
• Format: Article
• Language: English
• Subjects: Animals; Ethers, Cyclic - chemistry; Ethers, Cyclic - isolation & purification; Ethers, Cyclic - toxicity; Fishes; Harmful Algal Bloom; Mice; New Zealand; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Spectrophotometry, Ultraviolet
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja212116q

A novel marine toxin, brevisulcenal-F (KBT-F, from karenia brevisulcata toxin) was isolated from the dinoflagellate Karenia brevisulcata. A red tide of K. brevisulcata 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 K. brevisulcata showed potent mouse lethality and cytotoxicity, and laboratory cultures of K. brevisulcata 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.