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Chemical Studies on Marine Biotoxins

海洋生物毒素的化学研究

基本信息

批准号：
01470128
负责人：
ISOBE Minoru
金额：
$ 3.71万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1990
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-01470128/
关键词：
Biotoxins DSP activity Okadaic acid Puffer poison Tetrodotoxin Cyclic guanidine Cancer Promoter Inhibitor of protein phosphatase 生物トキンン下痢性貝毒

项目摘要

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.

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。本项目分为两部分，涉及两种天然产物冈田酸和河豚毒素的基础研究。已知冈田酸具有DSP活性，并且对蛋白磷酸酶具有抑制活性。合成了O-软海绵酸的东半分子（EHOK），并与软海绵酸进行了生物活性比较。EHOK对蛋白磷酸酶无活性（小于1/100）。而EHOK与OKA抗体有较强的结合活性，可用于DSP的检测。Yasumoto教授告诉我们，EHOK的结合强度实际上是OKA的8倍。OKA部分类似物的两个独立的生物学结果表明，冈田酸分子被分子中不同部分的系统识别。由于我们之前已经报道了环己烷部分，目前的目标是两者的组合。从纤维素的热解产物出发，利用其溴代衍生物进行Diels-Alder环加成反应。不稳定的溴代酮转化为稳定的乙烯基磷酸酯，有望促进TTX的全合成。将继续进行进一步的生物有机研究。