Formal synthesis of (+)-brefeldin A: application of a zinc-mediated ring expansion reaction.
An efficient formal synthesis of (+)-brefeldin A was accomplished through a synthetic approach that relied upon three keys steps. The five-membered ring was generated in a stereocontrolled fashion through application of a tandem conjugate addition-intramolecular cyclization method developed by Toru. Ring-closing metathesis provided access to a twelve-membered beta-keto lactone, which was ring-expanded to the alpha,beta-unsaturated-gamma-keto lactone through a zinc carbenoid-mediated reaction. Conversion of this lactone to (+)-brefeldin A has been reported previously.
Lin
Weimin
W
Department of Chemistry, University of New Hampshire, Durham, New Hampshire 03824, USA.
Zercher
Charles K
CK
D020126:Brefeldin A / Q000138:chemical synthesis*; D003500:Cyclization; D010084:Oxidation-Reduction; D015032:Zinc / Q000737:chemistry*
D020126:Brefeldin A; D015032:Zinc