What are Anomers?

Anomers are the two stereoisomers that result from different alternative stereochemistry at its anomeric center. Anomers are epimers of cyclic monosaccharides or glycosides that vary in the configuration of C-1 from one another.

Characteristics of Anomers

An anomer is a form of geometric variation found in carbohydrate molecules at the specific atom. A stereoisomer that varies in configuration at each stereo genic center is called an epimer. In a cyclic saccharide, an anomer is an epimer at the hemiacetal/hemiketal carbon, also known as the anomeric carbon. The carbon derived from the carbonyl carbon compound (functional group either ketone or aldehyde) of the open-chain form of the carbohydrate molecule is known as the anomeric carbon. The method of converting one anomer to the other is known as  anomerization. Different anomers have different physical properties, melting points, and precise rotations, as is typical of stereoisomeric compounds.

Naming of Anomers

Two anomers are designated alpha (α) or beta (β), according to the configurational relationship between the anomeric centre and the anomeric reference atom, hence they are relative stereo descriptors. The anomeric centre in hemiacetals is the anomeric carbon C-1. In hemiketals it is the carbon derived from the carbonyl of the ketone (e.g. C-2 in D-fructose). In the aldohexoses the anomeric reference atom is the stereocenter that is farthest from anomeric carbon in the ring (the configurational atom, defining the sugar as D or L). For example, in α-D-glucopyranose the reference atom is C-5.

If in the cyclic Fischer projection the exocyclic oxygen atom at the anomeric center is cis (on the same side) to the exocyclic oxygen attached to the anomeric reference atom (in the OH group) the anomer is α. If the two oxygens are trans (on different sides) the anomer is β. Thus, the absolute configurations of the anomeric carbon and the reference atom are the same (both R or both S) in the α anomer and opposite (one R and the other S) in the β anomer.

Anomerization

The method of converting one anomer to the other is known as anomerization. Anomerization of reducing sugars is known as mutarotation, and it occurs readily in solution and is catalyzed by acid and base. This reversible phase usually results in an anomeric mixture, with the two single anomers ultimately reaching equilibrium. The ratio of the two anomers is unique to the sugar in question. A solution, for example, would eventually become a mixture of approximately 64 per cent D-glucopyranoside and 36 per cent D-glucopyranose, regardless of the configuration of the starting D-glucose. The optical rotation of the mixture varies as the ratio changes; this effect is known as mutarotation.

Mode of anomerization

Despite the fact that cyclic sugar types are normally preferred, hemiacetals in aqueous solution are in equilibrium with their open-chain counterparts. The hemiacetal bond between C-1 (the carbon bound to two oxygens) and C-5 oxygen is cleaved (forming the open-chain compound) and reformed in aldohexoses to achieve this equilibrium (forming the cyclic compound). The OH group on C-5 can attack either of the two stereo chemically distinct sides of the aldehyde group on C-1 when the hemiacetal group is reformed. The α- or β-anomer depends on which side it attacks. Glycoside anomerization is most common in acidic environments. Protonation of the exocyclic acetal oxygen, ionization to form an oxocarbenium ion with the release of alcohol, and nucleophilic attack by alcohol on the reverse face of the oxocarbenium ion, followed by deprotonation are the typical steps in anomerization.

Properties of Anomers

Since anomers have different structures, they have different stabilizing and destabilizing effects. The anomeric effect, which stabilizes an anomer with an electron withdrawing group (typically an oxygen or nitrogen atom) in axial orientation on the ring, is one of the most important factors in its stability. In polar solvents like water, this effect is lost. 1,3-diaxial interactions, which normally destabilize an anomer with an axially oriented anomeric group on the ring. In pyranoses and other six-membered ring compounds, this effect is particularly evident. In the case of water, this is a significant factor. The anomeric group forms hydrogen bonds with other groups on the ring, resulting in the anomer's stabilization.

 Destabilization of the anomer occurs due to the dipolar repulsion between the anomeric group and other groups on the ring. In water, the β-anomer of D-glucopyranoside is the more stable anomer. The α-anomer of D-mannopyranose is the more stable anomer. Since anomers are diastereomers, their physical and chemical properties are often different. The exact rotation, which can be measured using polarimetry, is one of the most significant physical properties used to study anomers.

Effects of Anomers

Stereo electronic effects around the ring affect carbohydrate conformation and the relative stability of anomers.  For example, steric considerations may predict that the form of glucose and mannose will predominate because it maximizes the spacing between hydroxyl groups. Although the β-anomer population is higher than the α-anomer population in glucose (62 per cent vs. 38 per cent), the difference is smaller than would be anticipated. The α-anomer, on the other hand, is the most common type of mannose monosaccharide (64 per cent). The relative orientations of the bonding, nonbonding, and antibonding orbitals can be used to describe these relative proportions. In a simplified sp3 hybridization model, the in-ring O5 has two nonbonding orbitals in the axial and equatorial positions. The antibonding orbital of an axial C1 hydroxyl will overlap in phase with the axial portion, stabilizing the configuration over the equatorial anomer.

 The relative dipole vectors of the O5 nonbonding orbitals and the dipole of the polarized C1–O1bond can also be used to explain the anomeric or Edward–Lemieux effect. These dipoles are in opposite orientations in the α-anomer, resulting in a low-energy state, while they are more aligned in the equatorial position, resulting in a less energetically favorable state. The C2–O2 -bond is also located in the axial configuration in mannose, which is the C2 epimer of glucose, and preferentially stabilizes the axial anomer.

Context and Applications

This topic is significant in the professional exams for both undergraduate and graduate courses, especially for           

• Bachelors in Chemistry
• Masters in Chemistry

Related Concepts   

Stereo electronic Effects, Carbohydrate-Mediated Interactions