Enantioselective total synthesis of brevetoxin A: convergent coupling strategy and completion.
A highly convergent, enantioselective total synthesis of brevetoxin A is reported. The development of a [X+2+X] Horner-Wadsworth-Emmons/cyclodehydration/reductive etherification convergent coupling strategy allowed a unified approach to the synthesis of two advanced tetracyclic fragments from four cyclic ether subunits. The Horner-Wittig coupling of the two tetracyclic fragments provided substrates that were explored for reductive etherification, the success of which delivered a late-stage tetraol intermediate. The tetraol was converted to the natural product through an expeditious selective oxidative process followed by methylenation.
Crimmins
Michael T
MT
University of North Carolina at Chapel Hill, Department of Chemistry, Chapel Hill, NC 27599-3290, USA. crimmins@email.unc.edu
Zuccarello
J Lucas
JL
McDougall
Patrick J
PJ
Ellis
J Michael
JM
D002384:Catalysis; D003500:Cyclization; D004988:Ethers, Cyclic / 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; D000095702:Polyether Toxins
D004988:Ethers, Cyclic; D008387:Marine Toxins; D035964:Oxocins; C076262:Brevetoxin A; D000095702:Polyether Toxins