68(P45) 麻痺性貝毒ゴニオトキシン類のチオールによる還元的変換 : 反応中間体の同定とその反応機構について(ポスター発表の部)

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Gonyautoxins 1-4 (GTXs) are 11-O-sulfated analogues of saxitoxins (STXs). These compounds block voltage-gated sodium channels at very low concentration and cause paralytic shellfish poisonings. GTXs have been shown to be transformed reductively into STXs by homogenates of accumulating organisms or by bacteria. On the other hand, mild chemical treatment of GTXs with thiol reagents such as glutathione or 2-mercaptoethanol also results in the formation of STXs. Although the machanism of these transformations have risen intriguing questions, no detailed study has been conducted. Herein, we describe for the first time, isolation and characterization of stable intermediates, 11-sulfide of STXs, formed in the course of reductive transformations of GTXs by thiols, and propose the mechanism of these unusual conversion to be "two step" reactions. These steps include (a) replacement of O-sulfate by a thiol reagent to give a thioether inter mediate, and (b) attack of another thiol at the sulfur atom of the inter mediate to give the products, STX and a disulfide. The proposed mechanism in the above reductive transformation is reminiscent of several enzymatic reduction processes, such as reductive cleavage of carbon-nitrogen bond catalyzed by glycine reductase, proline reductase or reduction of tetrachlorohydr oquinone (TCHQ) by TCHQ dehalogenase. Discovery of stable 11-thiol derivatives allowed us to develop biochemical probes, which would facilitate not only the study of the more detailed mechanisms of the transformation and dynamics of these toxins in nature, but also to confirm STX binding mechanisms in the voltage-gated sodium channel.
天然有機化合物討論会の論文
1999-09-01

68(P45) 麻痺性貝毒ゴニオトキシン類のチオールによる還元的変換 : 反応中間体の同定とその反応機構について(ポスター発表の部)

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