Enantioselective total synthesis of brevetoxin A: unified strategy for the B, E, G, and J subunits

Chemistry. 2009 Sep 14;15(36):9223-34. doi: 10.1002/chem.200900776.

Abstract

Brevetoxin A is a decacyclic ladder toxin that possesses 5-, 6-, 7-, 8-, and 9-membered oxacycles, as well as 22 tetrahedral stereocenters. Herein, we describe a unified approach to the B, E, G, and J rings based 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 completion of a convergent synthesis of brevetoxin A.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alkylation
  • Cyclization
  • Ethers / chemical synthesis*
  • Ethers / chemistry
  • Marine Toxins / chemical synthesis*
  • Marine Toxins / chemistry
  • Molecular Structure
  • Oxocins / chemical synthesis*
  • Oxocins / chemistry
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Ethers
  • Marine Toxins
  • Oxocins
  • Brevetoxin A