Abstract
Gambierol was isolated as a neurotoxin from the cultured cells of the ciguatera causative dinoflagellate Gambierdiscus toxicus. The structure consists of a ladder-shaped trans-fused octacyclic ring system that includes 18 stereogenic centers and a partially conjugated triene side chain. Starting from the reaction of the left half ABCD fragment with the oxiranyl anion derived from an epoxy sulfone, we have achieved the total synthesis of gambierol. The salient features of the route include: i) direct carbon-carbon bond formation on an oxirane ring, ii) the subsequent sulfonyl-assisted 6-endo cyclization, and iii) a ring-expansion approach to seven-membered ether rings.
