Chapter 4 - Formation of the Glycosidic Linkage1–26

Abstract

In forming the glycosidic linkage, close attention must be paid to the orientation of the hydroxyl group at C2 of the glycosyl donor; there are several common scenarios. Indeed, the glycosidic linkage is formed from a glycosyl donor and a glycosyl acceptor. A glycosyl donor, of either the α- or the β-configuration, is treated with a glycosyl acceptor to form, by the elimination of HX, the disaccharide containing the new glycosidic linkage, of either the α- or the β-configuration at C1´. In the process, there is no change in configuration at C4 in the glycosyl acceptor. In less common circumstances, the glycosyl acceptor may react through the hydroxyl group of the anomeric (hemiacetal) center. In this case the formation of the glycosidic linkages results in the α- or β-configuration at both C1 and Cl´; the product is a nonreducing disaccharide. An example of such a disaccharide is trehalose. The formation of a glycosidic linkage will not be an easy task. Apart from the activation of the glycosyl donor, there are problems of the stereoselectivity (α- or β-) of the process and the access to just the desired hydroxyl group of the glycosyl acceptor (protecting group chemistry). Nature, of course, circumvents all of these problems with the use of enzymes, but for the synthetic carbohydrate chemist, much ingenuity, creativity, and hard work are necessary to match the rewards of evolution. The majority of methods available for the formation of the glycosidic linkage use a glycosyl donor that is a precursor of either an intermediate oxocarbenium ion (as part of an ion pair) or, at least, a species that has a significant positive charge at the anomeric carbon atom.