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

Abstract

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 C(107)H(160)O(38) 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 LD(50) (mouse i.p.) for KBT-F was 0.032 mg/kg.

Determination of the Absolute Configuration of Super‐Carbon‐Chain Compounds by a Combined Chemical, Spectroscopic, and Computational Approach: Gibbosols A and B

“…The presence of two tetrahydropyran moieties in III was revealed by isotope shift experiments measured in CD 3 OD and CD 3 OH . Four oxymethine carbon centers involved in ether linkage, that is, C43 ( δ =70.89), C47 ( δ =73.22), C51 ( δ =76.47), and C55 ( δ =75.75), did not exhibit deuterium‐induced isotope shift.…”

Synthesis-Driven Stereochemical Assignment of Marine Polycyclic Ether Natural Products

“…It should be emphasized, however, that the configurational assignment made by means of computational and/or bioinformatic approaches still needs to be confirmed through synthesis/NMR analysis of suitably designed model compounds and finally be established in an unambiguous manner by total synthesis. Significant challenges remaining in this area are the complete stereochemical assignments of extremely large polycyclic ethers, brevisulcenal-F [ 143 ] and prymnesins [ 144 , 145 ].…”

Development of New Synthetic Methods Using Oxiranyl Anions and Application in the Syntheses of Polycyclic Ether Marine Natural Products

“…Gymnocin-A (139) is a polycyclic ether isolated from cultured cells of the red-tide dinoflagellate Karenia mikimotoi by Satake et al 74) This complex polyether exhibits potent cytotoxicity (IC 50 = 1.3 µg/mL) against mouse leukemia P388 cells. A characteristic feature is the linear array of 14 contiguous trans-fused rings, which is the third-longest fused ring Chart 19.…”