Carbohydrate conformation, solvent effects

H. Greenberg and A. S. Perlin, 1,4 Dioxane-2,6-diol from anhydroalditols Solvent effects on its formation and conformation, Carbohydr. Res., 35 (1974) 195-202. 

Only some aspects of the solvent perturbation on the conformational properties of carbohydrate polymers have been covered in this chapter. One of the maj or concerns has been to develop a description of these solvent effects starting with the complex conformational equilibria of simple sugars. In fact, only recently it has been fully appreciated the quantitative relationship between conformational population and physical properties, e.g. optical rotation. 

Formation and migration of cyclic acetals of carbohydrates has been reviewed. Molecular mechanical calculations have been used to calculate the energies of various conformations of bicyclic acetals of C4-C6 alditols with formaldehyde. The thermodynamic stabilities of the [4.4.0] products were predicted to be higher than for the [5,3.0] products in the gas phase. Discrepancies with experimentally observed data were ascribed to solvent effects. 

The structures of carbohydrates have fascinated chemists since the dawn of modem organic chemistry with the work of Fischer. " While Fischer determined the stereochemical relationship of the simple sugars, controversy still remains as to some of the more subtle features of their three-dimensional structures. In particular, the origins of the anomeric and exo-anomeric effects remain topics of debate. Complicating these discussions is the role that solvent may play in perhaps preferentially stabilizing some conformer(s) over others. We will concentrate our attention in this section to stmcture of D-glucose and the role that aqueous solvent has in altering its eonformational preference. 

The extent to which this kind of calculation is able to predict the effect of the solvent on conformational properties of carbohydrates has been thoroughly tested on 2-substituted oxane derivatives, D-glucopyranose, and methyl a- and y -D-glucopyranoside. In the model applied, the cavity term in Eq. 7 is based on an expression taken from the Scaled Particle Theory, and the electrostatic term is calculated according to the reaction held theory. The dispersion term takes into account both attractive and repulsive nonbonding interactions by using a combination of Lx)ndon dispersion energy and Bom-type repulsion. ... 

We saw in Chapter 2 that glucose can cyclize to form either the a ox hemiacetal. All of the substituents on the tetrahydropyran ring of glucose are equatorial except for the hemiacetal hydroxyl group, which may be either axial (for the a anomer) or equatorial (for the 6 anomer). If the conformational preferences of the tetrahydropyran ring are similar to those of cyclohexane, then an A value for OH of 0.87 in a protic solvent would predict that the axial anomer should comprise no more than 10% of the mixture. Experimentally, it has been determined that the a anomer is present to the extent of 34% of the equilibrium population of conformers. In the case of o-marmose, the a anomer (10) is the major isomer, and the )3 anomer (11) comprises only 32% of the equilibrium mixture. This preference for axial conformer in carbohydrates has been termed the anomeric effect. This term is also used for any system R-Y-C-X, where X is an electronegative atom and Y is an atom with at least one lone pair. 

Solvent and temperature effects on optical rotation and conformation of model carbohydrates, J. Chem. Soc. Perkin II, 191. 

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