89 オカダ酸の構造活性相関(ポスター発表の部)

概要

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Marine organisms produce novel compounds with remarkable biological activitites. Our studies have been carried out in order to clarify function-fine structure interrelationship of the super-carbon-chain compounds such as okadaic acid (2). This super-carbon-chain compound exhibits marked in vitro cytotoxicity and causes diarrhetic shellfish poisoning. Interestingly, okadaic acid is a potent inhibitor of protein phosphatases 1 and 2A. Then, the conjugated form of okadaic acid with glycine, glycookadaic acid was proved to be an anticachexia substance. Our study toward elucidation of interrelationship between fine structure and activity was started. By the NMR data analysis, we proposed importance of the formation of a flexible cavity between C1 carboxyl group and C24 hydroxyl group. Based on the flexible cavity hypothesis (Fig. 1), C24 hydroxyl group was epimerized by reaction sequencing. Epimerization at C24 was reduced the cytotoxicity of okadaic acid by two orders of magnitude. Two corresponding epimers at C27 and C7 were obtained by chemical reactions. Experiment for cytotoxicity of these epimers is currently under way. Our flexible caivity hypothesis will be supported by the fact that two epimers does not work against L1210 tumor cells.
天然有機化合物討論会の論文
1993-09-10