Chemical Studies on Marine Biotoxins

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In the field of Biotoxins, the structral, analytical and synthetic studies on marine toxin are one of the significant subjects. The project has been separated into two parts, involving two natural product, okadaic acid and tetrodotoxin directed toward the basic research. Okadaic acid was known to have DSP activity, and to have inhibitory activity against protein phoshatase. We have synthesized the East Half molecule (EHOK) of O-Kadaic Acid and compared the biological activity of EHOK with okadaic acid itself. EHOK showed no activity (less than 1/100) to protein phosphatase when examined by Prof. Takai, a colaborator. EHOK, however, showed a strong binding activity with antibody of OKA, which was designed for DSP detection. Prof. Yasumoto reported us that EHOK binded in fact, 8 times as strongly as OKA. These two independent biological result with OKA partial analog suggested the okadaic acid molecule is recognized by those system with a different part in its molecule.In the synthetic works on Tetrodotoxin (TTX), we have concluded the synthesis of a molecule with cyclic guanidine of TTX. Since we have previously reported the cyclohexane moiety, the current target was the combination of the two. Starting from the pyrolysate of cellulose, we use its bromoderivative for Diels-Alder cycloaddition. The unstable bromo-ketone was converted into the stable vinyl phosphate, which was promising for promoting total synthesis of TTX. Further bioorganic studies will be continued.