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 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.
Crimmins
Michael T
MT
Univeristy of North Carolina at Chapel Hill, Department of Chemistry, Chapel Hill, NC 27599-3290, USA. crimmins@email.unc.edu
Ellis
J Michael
JM
Emmitte
Kyle A
KA
Haile
Pamela A
PA
McDougall
Patrick J
PJ
Parrish
Jonathan D
JD
Zuccarello
J Lucas
JL
D000478:Alkylation; D003500:Cyclization; D004987:Ethers / Q000138:chemical synthesis* / Q000737:chemistry; D008387:Marine Toxins / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D035964:Oxocins / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D000095702:Polyether Toxins
D004987:Ethers; D008387:Marine Toxins; D035964:Oxocins; C076262:Brevetoxin A; D000095702:Polyether Toxins