Influence of solvent on the magnitude of the anomeric effect

Abstract

This paper is dedicated to Dr. 0. E. (Ted) Edwards J.-P. PRALY and R. U. LEMIEUX. Can. J. Chem. 65, 213 (1987). A novel application of I3c nuclear magnetic resonance provided the effects of solvent polarity and hydrogen-bond formation on the conformational equilibria for a range of 2-substituted tetrahydropyrans and the results are interpreted in terms of how solvent affects the competition between the endo-and exo-anomeric effects in determining the magnitude of the anomeric effect. In accord with the generally accepted origin of the endo-and exo-anomeric effects (anti-periplanar n-a* interaction of the oxygen lone-pair orbital with the antibonding orbital of the adjacent C-0 bond), the exo-anomeric effect for the a anomer is expected to be weaker because charge delocalization from the glycosidic oxygen to anomeric center is in competition with delocalization from the ring-oxygen atom. The effects of solvent on the relative magnitudes of the endo-and exo-anomeric effects are then considered to arise from the formation of specific complexes with the solvent, and the exo-anomeric effect of a P-glycoside is more strongly influenced. It is contended that hydrogen bonding of solvent to the ring oxygen increases the exo-anomeric effects. For this reason water is particularly effective for the strengthening of the exo-anomeric effect and, thereby, the conformational rigidity of glycosides. Experimental evidence is presented that indicates that the anomeric hydroxyl groups of free sugars dissolved in water tend to prefer the equatorial orientation because these provide stronger hydrogen bonds as proton donors to water.

Glycogen phosphorylase: A multifaceted enzyme

“…8c), the cofactor phosphate acts as an acid to protonate the phosphate of glucose-l-phosphate and the C!-O1 bond has to be cleaved without direct protonation of the glycosidic oxygen. The conformation observed for heptulose-2-phosphate is similar to that predicted from stereoelectronic theory to weaken the exo-anomeric effect and promote cleavage of the alpha glycosidic bond (66). The theory predicts that an O-C bond in the grouping O-C-O is strongest (i.e.…”

Studies on the molecular recognition of synthetic methyl β‐lactoside analogs by ricin, a cytotoxic plant lectin

“…As previously discussed this conformational behaviour is in accordance with the solid state structure of Plactose [48], which is very close to conformer A, with the conformation in solution for 3C-enriched methyl fl-lactoside (l), also determined as conformer A on the basis of I3C-NMR data [%I; and with that of the disaccharide head group of 3-0-P-lactosyl-I ,2-O-tetradecyl-sn-glycerol which moves on the membrane surface in a conformation very close to C or C', according to 2H-NMR [54]. Conformer A would be favored by the exo-anomeric effect [62]. Either conformer A or B would permit the formation of hydrogen bonding between HO-3 and 0-5' which has been found to be present in the solid state structure of fl-lactose [48]; however, since this binding can not exist in compounds 4 or 6, it does not seem to be an essential requisite to determine the conformational preferences of these derivatives in solution.…”

Toward the origin of the conformational preference of 2-methoxyoxane, a model useful to study the anomeric effect

“…13 The form of this potential allowed us to explain the observations made by Fuchs et al 19 based on the statistic study of 111 samples containing the O-C-O-C segment. Due to the non-existence of the eq-1 conformer, and the fact that the anti-anti conformer of dimetoxymethane exists in its corresponding potential energy surface; makes this molecule inappropriate as a model to study the anomeric effect in the O-C-O segment.…”

“…The anomeric effect is indeed very sensitive to the solvent dielectric constant. 13 It has been observed that the axial conformational preference is increased in polar solvents under a variety of experimental conditions. Praly and Lemieux determined the solvent effect on the thermodynamic equilibria for 2-Me-THP and found ∆H o close to zero only in polar or hydrogen bonding solvents.…”