Chemical Studies on Marine Biotoxins

在生物毒素领域，海洋毒素的结构、分析和合成研究是一个重要的课题。该项目分为两部分，涉及两种天然产物冈田酸和河豚毒素，旨在进行基础研究。已知冈田酸具有DSP活性，并对蛋白磷酸裂解酶具有抑制活性。我们合成了O-卡达克酸的东半分子(EHOK)，并与冈田酸本身的生物活性进行了比较。经合作者高井教授检测，EHOK对蛋白磷酸酶无活性(低于1/100)。然而，EHOK与专为检测DSP而设计的OKA抗体具有很强的结合活性。Yasumoto教授告诉我们，EHOK实际上是有约束力的，是OKA的8倍。这两个独立的生物学结果与OKA部分相似，表明冈田酸分子被分子中不同部分的体系所识别。在河豚毒素(TTX)的合成工作中，我们完成了TTX环胍分子的合成。由于我们之前已经报道了环己烷的部分，目前的目标是两者的组合。从纤维素的热解产物出发，利用其溴代试剂进行Diels-Alder环加成反应。将不稳定的溴代酮转化为稳定的磷酸乙烯酯，有望促进TTX的全合成。将继续进行进一步的生物有机研究。

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.