The ability to control the glycosylation patterns in oligosaccharides and glycoconjugates is of great significance to the field of drug discovery, as this provides one of the most effective strategies for harnessing the physical and biological properties of various organic compounds. Many important molecular parameters might be greatly affected by the position and stereochemistry of the glycosidic linkages.  However, despite the recent advances in the fields of chemical synthesis and catalysis, we are still very limited in our ability to introduce such alternations. The assembly and attachment of even moderately complex oligosaccharides may suffer from a large number of steps, which often renders such studies impractical for the drug discovery. Not surprisingly, a number of the recent efforts have been focused on developing catalytic methods for the regioselective and chemoselective synthesis of oligosaccharides and glycoconjugates.  This presentation summarizes our efforts on achieving regioselective glycosylation of natural and unnatural polyols by employing chiral Bronsted acid-catalyzed reactions with carbohydrate-derived trichloroacetimidates. In particular, the use of chiral Bronsted acids to override the steric bias and introduce glycosylation at the less reactive sites will be discussed in the context of glycosylation of natural and unnatural 14-membered macrolactones. In addition, a complementary strategy based on a single pot traceless protection/glycosylation to achieve regioselective glycosylation of polyol-containing 14-membered macrolides and cardiotonic steroids will be presented.

Studies on regioselective glycosylation of natural polyols

255th National Meeting (2018)

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