Mechanistic studies and methods to prevent aglycon transfer of thioglycosides

J Am Chem Soc. 2006 Sep 6;128(35):11612-9. doi: 10.1021/ja063247q.

Abstract

Thioglycosides have been employed extensively for the synthesis of complex oligosaccharides, carbohydrate libraries, and mimetics of O-glycosides. While very useful, aglycon transfer is a problematic side reaction with thioglycosides. In this paper, a series of mechanistic studies are described. The aglycon transfer process is shown to affect both armed and disarmed thioglycosides, cause anomerization of the carbon-sulfur bond of a thioglycoside, and destroy the product of a glycosylation reaction. The results indicate that the aglycon transfer process can be a major problem for a wide range of thioglycosides. This side reaction is especially important to consider when carrying out complex reactions such as solid-phase glycosylations, one-pot or orthogonal multicomponent glycosylations, and construction of carbohydrate libraries. To prevent transfer, a number of modified aglycons were examined. The 2,6-dimethylphenyl (DMP) aglycon was found to effectively block transfer in a variety of model studies and glycosylation reactions. The DMP group can be installed in one step from a commercially available thiol (2,6-dimethylthiophenol) and is useable as a glycosyl donor. On the basis of these features, the DMP group is proposed as a convenient and improved aglycon for thioglycosides.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Energy Transfer
  • Glycosylation
  • Models, Chemical
  • Molecular Structure
  • Oligosaccharides / chemical synthesis*
  • Oligosaccharides / chemistry
  • Stereoisomerism
  • Thioglycosides / chemistry*

Substances

  • Oligosaccharides
  • Thioglycosides