Glucose anomeric effect

It IS not possible to tell by inspection whether the a or p pyranose form of a par ticular carbohydrate predominates at equilibrium As just described the p pyranose form IS the major species present m an aqueous solution of d glucose whereas the a pyranose form predominates m a solution of d mannose (Problem 25 8) The relative abundance of a and p pyranose forms m solution depends on two factors The first is solvation of the anomeric hydroxyl group An equatorial OH is less crowded and better solvated by water than an axial one This effect stabilizes the p pyranose form m aqueous solution The other factor called the anomeric effect, involves an electronic interaction between the nng oxygen and the anomeric substituent and preferentially stabilizes the axial OH of the a pyranose form Because the two effects operate m different directions but are com parable m magnitude m aqueous solution the a pyranose form is more abundant for some carbohydrates and the p pyranose form for others... 

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. 

Much of the computational literature of glucose pertains to the ratio of the two anomers. This is formulated as the anomeric effect the stability of the a anomer, with its axial group, over the expectedly more stable p anomer, where the hydroxyl group occupies the equatorial position. This has been rationalized in two ways (1) minimizing the dipole-dipole repulsion because of the C-O bonds or (2) hyperconjugative stabilization by donation of the ring oxygen lone pair... 

The dispiroketal protection of monosaccharides is controlled by the stabilizing influence of multiple anomeric effects leading to a single diastereomeric derivative. In certain examples, where there is more than one diequatorial diol pair present in the molecule, as for example in D-glucose derivatives, reaction affords a mixture of diacetals (O Scheme 22). The reaction, often giving crystalline compounds, is carried out by treatment of the polyol with 3,4,3, 4 -tetrahydro-6,6 -bis-2H-pyran in chloroform at reflux in the presence of a catalytic amount of CSA[151]. 

An additional role for aromatic groups in carbohydrate binding may be to stabilize the exo-anomeric effect [20]. The exo-cyc c 01 lone pair of a pyranose (e. g., glucose) can donate electron density into the C1-05 cr orbital while decreasing electron density in the C1-05... 

As we would expect for dipole-dipole interactions, the anomeric effect weakens as the polarity of the solvent increases (Sec. 9.10). For free sugars dissolved in water, the anomeric effect is usually outweighed by other factors D-glucose, for example, exists predominantly as the )S-anomer, with the —OH on C-1 equatorial. 

The anomeric effect is solvent and substituent dependent and decreases in the following order Cl > OAc > OMe > OH, as exemplified by the equilibrium concentrations of the a and (3 anomers of substituted D-glucose in various protic solvents at 25... 

A detailed study of trichloroacetonitrile addition to 2,3,4,6-tetra-O-benzyl-D-glucose showed that from the 1-oxide the -trichloroacetimidate is formed preferentially or even exclusively in a very rapid and reversible addition reaction (Scheme 16). However, this product anomerizes in a slow, base-catalyzed reaction via retroreaction, 1-oxide anomerization and renewed addition) practically completely to the a-trichloroacetimidate, with the electron-withdrawing 1-substituent in an axial position as favored by the thermodynamically efficient anomeric effect. Thus with different bases, for instance K2CO3 and... 

As one of a number of such examples, the a-form of d-glucose (36%) is more abundant with respect to the fi-form (64%) than expectations based on substituents in cyclohexane would indicate. This unexpected abundance of the a-form is known as the anomeric effect,... 

In some sugars, e.g. D-glucose, and 2-alkoxytetrahydropyrans, the axial form is populated to a greater extent than the axial population of the corresponding cyclohexane would suggest. This is known as the anomeric effect and two possible contributory factors were discussed. 

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