Synthesis of the I-K Fused Polyether Array of CTX3C and Related Ciguatoxins by Use of a Gold-Catalyzed Cyclization Reaction.

The I-K fragment (C31-C49) of the ciguatoxin CTX3C has been synthesized from a simple chiral pool derived tetrahydropyranyl alcohol. An efficient gold-catalyzed cyclization reaction of a γ'-hydroxy ynone has been used to accomplish efficient closure of ring K under mild conditions. The resulting vinylogous ester has been elaborated to give a complete tricyclic fragment bearing the dimethyl-substituted side chain required for assembly of the LM spirocyclic acetal portion of the target.