Total Synthesis of Ciguatoxins and Studies on The Antibodies and The Mechanism of Action

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Ciguatera poisoning is an important medical issue in the tropical and subtropical regions. The first total synthesis of ciguatoxin CTX3C, one of the causative toxins, through "unified convergent strategy, i.e., [X+2+Y] polyether assembly" was accomplished in 2001.1.We then have developed the practical second-generation total synthesis of CTX3C.2.Moreover, we have successfully applied it to synthesize 51-HydroxyCTX3C and CTX1B. Further methodological improvements allowed us to prepare a few mg of CTX3C and 51-HydroxyCTX3C, respectively, which be used for interdisciplinary researches.3.Highly sensitive monoclonal antibody 8H2 was developed against CTX1B, 51-HydroxyCTX3C, and so on.4.Sandwich Immunoassay using mAbs 8H2 and 10C9 was able to detect 51-HydroxyCTX at the level of pg/ml.5.Sandwich immunoassay using mAbs 10C9 and 3D11 detected CTX3C in ciguateric fish caught in the Okinawa sea area.6.Mice poisoned with CTX3C were cured by monoclonal antibodies we developed, which will be applied for humans. In addition, vaccines for ciguatera poisoning would be developed.7.The central 9-membered F ring of ciguatoxins is proved to be crucial for their toxicity.8.Synthetic ciguatoxins and bio-probes such as the conjugates with biotin will unveil the VSSC-ligand interaction at the atomic lebel and the gating mechanism.