Total synthesis of ciguatoxin CTX3C

Ciguatoxins are the causative neurotoxins of ciguatera seafood poisoning, and more than 20,000 people suffer annually from ciguatera disease in subtropical and tropical regions. The extremely low content of ciguatoxins in fish has hampered the isolation and detailed biological studies. The complicated and huge, 3 nm long, molecular structure of ciguatoxins has impeded synthetic chemists from completing their total syntheses, which are formidable synthetic challenge in modern organic synthesis. Our highly convergent strategic approach featuring the chemoselective ring closing metathesis (RCM) reaction as a key tactics, (i) alkylative coupling and RCM, (ii) intramolecular carbonyl olefination and reductive etherification, (iii) chemo- and regioselective radical cyclization and RCM, has enabled the first total synthesis of ciguatoxin CTX 3 C, which will provide the practical supply for further studies.