Ciguatera is a widespread human scale food poisoning that is caused by fishes dwelling in coral reefs in the tropics and subtropics. Ciguatoxis (CTX1B, 1 and CTX3C, 2), regarded as the principal toxins of ciguatera, were isolated from the moray eel, Gymnothorax javanicus, and the absolute configuration of 1 was determined as shown in Figure 1. Synthesis of ciguatoxins has recieved considarable attention among synthetic chemists due to the striking feature and biological features of these toxins. We developed a new method useful for constructing polycyclic ether systems based on alkylation and ring-closing metathesis reaction, and successfully synthesized the ABCDE ring moieties of ciguatoxin using this technique strating with the iodide 4 and ester 5 corresponding to the AB and E ring, respectively. Alternatively, we synthesized the IJKLM ring fragment via successive esterification of the alcohol 23 and carboxylic acid 24, Tebbe olefination, and ring-closing metathesis sequences, and the chemo- and stereoselective reduction of the methyl acetal. Studies toward total synthesis of ciguatoxin are currently underway.
