Conformational domino effect in saccharides. 2. Anomeric configuration control.

A series of alkyl beta-D-glucopyranosyl-(1-->6)-alpha-D-glucopyranosides were synthesized and analyzed by NMR and CD techniques. As in their beta-anomer series, the rotational populations of the hydroxymethyl group involved in the interglycosidic linkage (torsion angle omega) are shown to depend on the aglycon and the solvent. However, for this alpha-anomer series the rotational dependence arises directly from steric effects. Correlations between rotational populations and molar refractivity (MR) steric parameters, but not Taft's steric parameters (beta-anomers), of the alkyl substituents were observed. The conformational domino effect previously predicted from alkyl beta-(1-->6)-diglucopyranosides is now supported by the conformational properties of their alpha-anomers, the anomeric configuration controlling the domino effect. In addition, the rotational populations around the C5'-C6' bond (torsion angle omega') depend weakly on the structure of the aglycon and the anomeric configuration.

Conformational domino effect in saccharides: a prediction from alkyl beta-(1-->6)-diglucopyranosides.

A series of alkyl beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosides, containing nonchiral and chiral aglycons, were synthesized and analyzed by NMR and CD. The results, collected from four sets of disaccharides, demonstrated that the rotational properties of the interglycosidic linkage depend on the structural natures of both the aglycon and the solvent. Stereoelectronic and steric factors explain this rotational dependence, the gauche- trans (gt) rotamer being the most stable. Furthermore, correlations between Taft's steric parameters or between the pKa values of the alkyl substituent (aglycon) versus corresponding rotamer populations were observed. These results point to a natural conformational domino effect in oligosaccharides, where the conformational properties of each (1-->6) interglycosidic linkage will depend on the structure of the previous residue or its aglycon. In addition, a very weak rotational population dependence of the hydroxymethyl group at residue II on the aglycon at residue I was observed. The population of the gauche- gauche (gg) rotamer decreased, and that of gt increased as the Taft's steric parameters of the remote aglycon increased, independently of the disaccharide series and of the solvent.

Hydroxymethyl rotamer populations in disaccharides.

Sixteen methyl glucopyranosyl glucopyranoside disaccharides (methyl beta-d-Glcp(p-Br-Bz)-(1-->x)-beta/alpha-d-Glcp) containing beta-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)- (beta series), to (1-->6)-, to (1-->2)- (alpha 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%.