A double regio- and stereoselective glycosylation strategy for the synthesis of N-glycans

Chemistry. 2008;14(4):1304-11. doi: 10.1002/chem.200701251.

Abstract

A building block approach for biantennary N-linked oligosaccharides from glycoproteins (N-glycans) has been developed. Starting from a core trisaccharide (beta-mannosyl chitobiose) containing a benzylidene-protected beta-mannoside, the attachment of the disaccharide building blocks for the antennae can be performed in a double regio- and stereoselective manner. A short synthesis of a GlcNPhtbeta1,2Man donor was developed. The benzylidene acetal moiety, as a minimal protection of the beta-mannoside, allows selective alpha-glycosylation at OH-3 of the 2,3-diol with GlcNbeta1,2Man trichloroacetimidate donors. Subsequent debenzylidenation leads to a 4,6-diol, which can be selectively extended at OH-6. Overreaction at OH-4 was generally low when phthalimido-protected donors were used. This general strategy represents a modular synthesis of N-glycans and their glycoconjugates.

MeSH terms

  • Carbohydrate Sequence
  • Glycoproteins / chemical synthesis*
  • Glycoproteins / chemistry*
  • Glycosylation
  • Imidoesters / chemistry
  • Mannosides / chemistry
  • Molecular Sequence Data
  • Oligosaccharides / chemical synthesis
  • Stereoisomerism
  • Substrate Specificity

Substances

  • Glycoproteins
  • Imidoesters
  • Mannosides
  • Oligosaccharides