40 シガトキシンの全合成と構造活性相関(口頭発表の部)

概要

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With their imposing molecular structure, the ladder-shaped polyethers including ciguatoxins pose considerable challenge to synthetic chemists. Ciguatoxins are isolated as the causative toxins of ciguatera seafood poisoning. Previously, we reported the total synthesis of CTX3C (2) and 51-hydroxyCTX3C (3), two representative congeners of ciguatoxins. In this presentation, we report the first total synthesis of CTX1B (1), which has one of the most complex structures among ciguatoxins. The SAR study of synthetic ciguatoxins is also discussed. Recently, we have developed two methods to synthesize the polyether compounds based on forming a O,S-acetal from a secondary alcohol and a halosulfide. The O,S-acetal was used as radical donor to cyclize the seven-memberd ether ring with an acrylate. Alternatively, the enol ether that was prepared from O,S-acetal was utilized as a radical acceptor to form ether ring. By using these two free radical approaches, CTX1B (1) was assembled in a concise and efficient fashion. To elucidate the biological mechanism of ciguatoxins, we performed the SAR study of the synthetic intermediates of CTX3C (2) and 51-hydroxyCTX3C (3). The SAR study clearly indicated that the semi-rigidity of the central portion of ciguatoxins was extremely important for its potent biological activity.
天然有機化合物討論会の論文
2006-09-15