Experimental and theoretical study of the O3/O4 regioselectivity of glycosylation reactions of glucopyranosyl acceptors

Abstract

The knowledge of the regioselectivity between different hydroxyl groups of glycosyl acceptors is valuable in planning simple strategies for the synthesis of oligosaccharides, minimizing the use of protecting groups. With the aim of obtaining deeper knowledge on this subject, we analyzed the relative reactivity of the OH-3 and OH-4 groups of 2,6-di-O-protected methyl α- and β-glucopyranosides in glycosylation reactions. The glycosyl acceptors were prepared by simple procedures, and galacto-pyranosyl and furanosyl trichloroacetimidates were evaluated as glycosyl donors. Experimental results were contrasted with those obtained by a molecular modeling approach. A fair agreement of the molecular modeling and experimental results was obtained. It has been shown, that by choosing the right anomer and protecting group, either the 1 → 3 or 1 → 4 linkage can selectively be installed using the appropriate glucosyl acceptor.