Influence of substitution at the 5α-Position on the side chain conformation of glucopyranosides.

We describe the preparation of methyl 5α-methyl-α-d-glucopyranoside and of 5α-fluoro-β-d-glucopyranose per acetate and the NMR-based conformational analysis of their side chains. Both the 5α-methyl and 5α-fluoro substituents increase the population of the gauche,gauche side chain conformer to the extent that it becomes the predominant conformation. In the 5α-methyl series this is attributed to steric effects, whereas in the 5α-fluoro series the optimization of attractive gauche effects is the more likely reason.