Nucleophilic Aromatic Substitution—A Possible Key Step in Total Syntheses of Vancomycin


  • K. B. thanks The National Institutes of Health for an NIH Research Career Development Award, and The Alfred P. Sloan Foundation for a Fellowship. C. M. thanks The National Institutes of Health for a predoctoral fellowship. Abbreviations: TFA = trifluoroacetic acid, TFAA = trifluoroacetic anhydride, BOC = tert-butyloxycarbonyl.


original image

How one of the major obstacles to a total synthesis of vancomycin 1, R = sugar, might be overcome has been demonstrated by Zhu et al. and others. They have used nucleophilic aromatic substitution reactions for biaryl ring formation and concomitant ring closure. Conditions for this transformation are sufficiently mild that it can be applied to form complex macrocycles like the 16-membered rings of vancomycin.