48 シガトキシンとその類縁体の構造(口頭発表の部)  [in Japanese] 48 Structures of Ciguatoxin and its Congener  [in Japanese]

Ciguatoxin (CTX) is the principal toxin of ciguatera, which is a fish poisoning of a dinoflagellate origin. The toxin (0.35mg) was isolated from the moray eel Gymnothorax javanicus and its less polar congener (0.74mg) from the causative organism, Gambierdiscus toxicus. We successfully elucidated their structures, 1 and 2 only by spectroscopic methods. High resolution FABMS suggested the formula of CTX to be C_<60>H_<86>O_<19>. The structure elucidation was carried out using the ^1H-^1H 2D-NMR methods. Although most proton connectivity was elucidated by ^1H-^1H COSY, the skeletal chain was interrupted at the following four positions; 1) protons (H23-H30) on a middle-membered ring that presumably undergoes a slow conformational change; 2) a methyl-bearing methine at the heavily overlapping region of ^1H NMR spectra (H-39); 3) a quaternary carbon bearing a methyl and a oxygen (C33); 4) a spiro-ketal carbon (C52). The first part was assigned by 2D-NMR measurements at ?25℃, which revealed the presence of a 9-membered ether-ring. The second part was clarified by simulating the decoupling difference spectrum using the coupling constants obtained from MM2 calculations. The third and last parts were solved by detecting NOE's at ?25℃ on Me-56/H37, Me-60/H-53 or H-48/H-55 and by DQF COSY, which showed a long range coupling between H-32 and Me-56. ^1H NMR assignments of 1 and 2 are shown in Table I. The structure, 1, partly resembles those of brevetoxins or yessotoxin. However, toxicity (0.35ug/kg, mice, ip.) of CTX is several hundreds times more potent than those of the other two toxins. The difference in activities is an interesting subject for future studies on structure-activity relationship among the compounds of this class.