Enantioselective Total Synthesis of Brevetoxin A: Unified Strategy for the B, E, G, and J Subunits

Brevetoxin A is a decacyclic ladder toxin that possesses five-,six-, seven-, eight-, and nine-membered oxacycles, as well as 22 tetrahedral stereocenters. Herein, we describe a unified approach to the B, E, G, and J rings predicated upon a ring-closing metathesis strategy from the corresponding dienes. The enolate technologies developed in our laboratory allowed access to the precursor acyclic dienes for the B, E, and G medium ring ethers. The strategies developed for the syntheses of these four monocycles ultimately provided multigram quantities of each of the rings, supporting our efforts toward the convergent completion of brevetoxin A.