Mechanistic Studies and Methods To Prevent Aglycon Transfer of Thioglycosides

Publisher Website
Google Scholar
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.