Y. Hashimoto, Tomotoshi Okaichi
Nov 1, 1960
Citations
0
Influential Citations
23
Citations
Journal
Annals of the New York Academy of Sciences
Abstract
Among anglers it has been a well-known fact that some carnivorous insects, such as the fly and ant, die from contact with the dead body of a marine annelid, Lumbricoiaereis heteropoda Marenz, which is commonly used as a bait. In 1934 Nitta' isolated a neurotoxic principle from this worm and named it nereistoxin. It was obtained in faintly yellow crystals of hydrogen oxalate (m.p. 178-180" C.) of unpleasant odor, soluble in fat solvents and insoluble in water. From analyses of hydrogen oxalate and picrate (m.p. 170" C.), the empirical formula was postulated to be C5H9NSz. Little knowledge was obtained on the functional groups, whereas it was found that the toxin responds to most alkaloid reagents, reduces the Fehling and ammoniacal silver nitrate solutions, and loses toxicity when treated with potassium permanganate. Nitta, however, turned his attentions to the pharmacological aspects, giving no further consideration to the chemical ones, which have been left untouched by scientists thus far. By using about 10 species of test animals from monkey to fly, Nitta2 concluded that the toxin exerts a strong action, chiefly on the nervous system, and slightly affects the internal organs and blood. I n injected animals, myosis, enhanced movement of the intestinal smooth muscle, shedding tears, and slavering were observed as typical symptoms. The small dose accelerated heart action, whereas the large dose repressed it; the repression effect was somewhat diminished by atropine. The lethal dose was 0.38 mg./lO gm. for mice and 1.8 mg./kg. for rabbits in subcutaneous injection. Recently, Matsue and Hirayamat reported that fish are more susceptible than warm-blooded animals, and the toxicity for fish is considerably enhanced by adjusting the medium to the alkaline side. I n light of the increasing importance of organic sulfur compounds in biological materials3 and the striking peculiarity of the empirical formula of nereistoxin, we recently commenced this study. Results thus far obtained in elemental analyses, qualitative tests on functional groups, estimation of ultraviolet and infrared absorption spectra, and reduction with sodium borohydride or Raney nickel have demonstrated that the toxin is a tertiary amine possessing a cyclic disulfide ring. These results have led us to postulate the possible structural formula, as discussed later, which has a 1 ,2-dithiolane moiety similar to 6: 8-thioctic acid (a-lipoic acid or 1,2-dithiolane-3-valeric acid), a member of the vitamin B group.