Structural studies on marine toxins

Abstract

The molecular structure of two toxic marine natural products were investigated. In Part One, 1.3 mg of ciguatoxin, the principal toxin of ciguatera poisoning, was isolated from viscera (50 kg) of the moray eel Gymnothorax javanicus. The substance has an extremely high toxicity (LD50) of 0.45 µg/kg by intraperitoneal injection into mice. Spectroscopic measurements were performed on the purified toxin with highly advanced instruments. By 252Cf-plasma desorption mass spectrometry molecular weight of 1112 was determined. A number of partial structures for the molecule were deduced from spectral data. These partial structures suggest that the molecule is essentially a highly oxygenated lipid. In Part Two, okadaic acid isolated from a Japanese marine sponge Halichondrai okadai, was investigated. The crystalline substance is cytotoxic monocarboxylic acid and has a molecular formula of C44H68O13 with a toxicity (LD50) of 192 µg/kg by intraperitoneal injection into mice. Spectroscopic and chemical studies indicated that the molecule is an ionophoric polyether, a class of compounds which is common in fungal metabolites but has not been found in marine organisms to-date. X-ray diffraction crystallography of the o-bromobenzyl ester was carried out and the structure 2 in Fig. 44 was given as the molecular structure of okadaic acid.