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

• Published in: Chemistry : a European journal Vol. 15; no. 36; pp. 9223 - 9234
• Main Authors: Crimmins, Michael T., Ellis, J. Michael, Emmitte, Kyle A., Haile, Pamela A., McDougall, Patrick J., Parrish, Jonathan D., Zuccarello, J. Lucas
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag 14.09.2009; Wiley
• Subjects: Alkylation; asymmetric synthesis; Chemistry; Chemistry, Multidisciplinary; chiral auxiliaries; Cyclization; Ethers - chemical synthesis; Ethers - chemistry; glycolate alkylation; Marine Toxins - chemical synthesis; Marine Toxins - chemistry; Molecular Structure; Oxocins - chemical synthesis; Oxocins - chemistry; Physical Sciences; ring‐closing metathesis; Science & Technology; Stereoisomerism; Structure-Activity Relationship; total synthesis; chiral auxiliaries; ORGANIC-SYNTHESIS; NATURAL-PRODUCTS; ASYMMETRIC ALDOL ADDITIONS; N-ACYL OXAZOLIDINONES; MARINE POLYCYCLIC ETHERS; OLEFIN METATHESIS; ring-closing metathesis; asymmetric synthesis; CONSTRUCTION; total synthesis; STEREOSELECTIVE-SYNTHESIS; glycolate alkylation
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.200900776

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. Piece by piece: A unified approach to the B, E, G, and J rings of brevetoxin A based upon a ring‐closing metathesis strategy from the corresponding dienes is described. The enolate technologies developed in our laboratory allowed access to the precursor acyclic dienes for the B, E, and G medium‐ring ethers (see scheme).