Structures and Configurations of Ciguatoxin from the Moray Eel Gymnothorax javanicus and Its Likely Precursor from the Dinoflagellate Gambierdiscus toxicus

TLDR: In this paper, the structure of ciguatera has been revealed to be a brevetoxin-type polyether comprising 13 continuous ether rings (7/6/6-7/7/9/7-6/8/6,7/8,6/7,6-spiro-5) with a molecular formula of CSOHMOI9.

Abstract: Ciguatoxin (CTX) is the toxic principle of ciguatera, which is responsible for the most widespread food poisoning of nonbacterial origin. The toxin, isolated from the moray eel Gymnothorax javanicus, and its congener, from the causative dinoflagellate Cambierdiscus toxicus, were used for this study. The structure elucidation was carried out by combined use of 'H NMR 2D correlation and NOE experiments done with no more than 0.35 mg of CTX and 0.74 mg of the congener. Broadening of 'H NMR signals due to a slow conformational change around a nine-membered ring was sharpened by measurements at -20 OC, in which all 'J proton connectivities and NOES around angular protons were clearly indicated. The structure of CTX, which had a molecular formula of CSOHMOI9, was disclosed to be a brevetoxin-type polyether comprising 13 continuous ether rings (7/6/6/7/7/9/7/6/8/6/7/6-spiro-5). The congener was shown to be a less oxygenated analogue of CTX. Their relative stereochemistries, except for C2 of CTX, were clarified by detailed analyses of IH NMR NOE experiments, MM2 energy calculations, and spectral simulations. Ciguatera is a term applied to food poisoning caused by in- gestion of coral reef fish. The worldwide occurrence of ciguatera not only endangers public health but also hampers local fisheries in subtropical and tropical regions. It is estimated that roughly 20000 people suffer annually from the poisoning, making it one of the largest-scale food poisonings of non-bacterial origins. The toxification mechanism of fish had not been known until one of the authors (T.Y.) identified an epiphytic dinoflagellate, Gambierdiscus toxicus, as a causative organism in 1977.' The