Interplay of Protecting Groups and Side Chain Conformation in Glycopyranosides. Modulation of the Influence of Remote Substituents on Glycosylation?

Abstract

The synthesis and conformational analysis of a series of phenyl 2,3,6-tri-O-benzyl-β-d-thio galacto- and glucopyranosides and their 6S-deuterio isotopomers, with systematic variation of the protecting group at the 4-position, are described. For the galactopyranosides, replacement of a 4-O-benzyl ether by a 4-O-alkanoyl or aroyl ester results in a small but measurable shift in side chain population away from the trans,gauche conformation and in favor of the gauche,trans conformer. In the glucopyranoside series on the other hand, replacement of a 4-O-benzyl ether by a 4-O-alkanoyl or aroyl ester results in a small but measurable increase in the population of the trans,gauche conformer at the expense of the gauche,gauche conformer. The possible modulating effect of these conformational changes on the well-known changes in the anomeric reactivity of glycosyl donors as a function of protecting group is discussed, raising the possibility that larger changes may be observed at the transition state for glycosylation. A comparable study with a series of ethyl 2,3,4-tri-O-benzyl-β-d-thioglucopyranosides reveals that no significant influence in side chain population is observed on changing the O6 protecting group.