Hydroxymethyl Rotamer Populations in Disaccharides

Abstract

Sixteen methyl glucopyranosyl glucopyranoside disaccharides (methyl β-d-Glcp(p-Br-Bz)-(1→x)-β/α-d-Glcp) containing β-glycosidic linkages (1→2, 1→3, 1→4, and 1→6) were synthesized and analyzed by means of CD and NMR spectroscopy in three different solvents. For each of these four types of disaccharides, a correlation was observed between the hydroxymethyl rotational populations around the C5−C6 bond of the glucopyranosyl residue II with the substituents and the anomeric configuration of the methoxyl group in residue I, as well as with the solvent. Nonbonded interactions, the stereoelectronic exo-anomeric effect, and hydrogen bonding were found to be responsible for the observed rotameric differences. Whereas the rotational populations of the (1→6)-linked disaccharides are mainly dependent on the exo-anomeric effect, the (1→2)-bonded disaccharides are strongly dependent on the anomeric configuration at C1, and the (1→3)- and (1→4)-linked disaccharides are mainly dependent on the substituents and the solvent. The population of the gt rotamer decreases as nonbonded interactions increase but increases as the exo-anomeric effect becomes greater, as well as in the presence of intramolecular hydrogen bonding to the endocyclic oxygen O5‘. Comparison of the hydroxymethyl rotational preferences between our model disaccharides revealed a dependence on the glycosidic linkage type. Thus the population of the gg and gt rotamers decreases/increases from (1→2)- (β series), to (1→6)-, to (1→2)- (α series), to (1→4)-, and to (1→3)-bonded disaccharides respectively, while the tg rotamer population remains almost constant (around 20%), except for the (1→3)- and (1→4)-linked disaccharides with the intramolecular hydrogen bonding to O5‘, where this population decreases to 10%.