The Conformation of Glucose

It was stressed in the previous section that the Haworth structures for the anomers of D-glucopyranose do not represent the true shape of the rings. The carbon atoms of glucose are all saturated, and the most stable form of a ring will be one that is strain free, i.e., where the angles formed by the bonds at each carbon atom are 109°, the tetrahedral angle. 

For simplicity, consider cyclohexane. Only two strain-free conformations are possible a chair and a boat, which, for clarity, are shown without H atoms  

There are 12 H atoms in the structure 6 are in the general plane of the rings and are called equatorial (e) 6 are perpendicular to the general plane of the rings and are called axial (a). 

The chair and boat forms are interconvertible by rotation around the C—C bonds. Therefore, they are not isomers, and the term conformers is used to describe the various shapes a molecule can possess. 

The difference in energy between the boat and chair conformers of cyclohexane is about 25kJmol I, which means that at 25°C only 1 in 1,000 molecules exists in the boat conformation. 

---

The 1,3-diaxial interaction between a C-1 hydroxyl group and the axial protons at C-3 and C-5 also operates in favour of fS-anomers. The resulting effect is that about 36% of D-glucose in equihbrium is present in the form of the a-anomer (at 20 °C). The conformation of glucose molecules explains the almost universal role of glucose in Hving systems as a structural unit of many biopolymers and an intermediate in a number of important reactions. 

Cyclodextrins are macrocyclic compounds comprised of D-glucose bonded through 1,4-a-linkages and produced enzymatically from starch. The greek letter which proceeds the name indicates the number of glucose units incorporated in the CD (eg, a = 6, /5 = 7, 7 = 8, etc). Cyclodextrins are toroidal shaped molecules with a relatively hydrophobic internal cavity (Fig. 6). The exterior is relatively hydrophilic because of the presence of the primary and secondary hydroxyls. The primary C-6 hydroxyls are free to rotate and can partially block the CD cavity from one end. The mouth of the opposite end of the CD cavity is encircled by the C-2 and C-3 secondary hydroxyls. The restricted conformational freedom and orientation of these secondary hydroxyls is thought to be responsible for the chiral recognition inherent in these molecules (77). 

It functions by generating a gated pore in the membrane to permit passage of glucose the pore is conformationally dependent on the presence of glucose and can oscillate rapidly (about 900 times/s). 

As shown in the chapter by French, Rowland and Allinger, when the same, relatively rigid glucose residue appears in numerous crystalline environments, there are substantial differences in the conformation. Of course, the errors in the experimental determination must also be considered. 

The alternative chair conformation, should we draw it instead, would be less favoured than that shown because of the increased number of axial substituents. The conformation of o-glucose is the easily remembered one, in that all the substituents are equatorial. 

In the case of glucose, the mutarotation gives 36 percent a, 64 percent p, and negligible strciight chain. The unequal distribution of the two anomers is due to the fact that the -OH on the anomeric carbon of the p form is equatorial, which for a chair conformer is more stable. The -OH on the anomeric carbon in the a anomer is axial, which means this anomer is slightly less stable. 

C. McDonnell, O. Lopez, P. Murphy, J. G. Fernandez Bolanos, R. Hazell, and M. Bols, Conformational effects on glycoside reactivity Study of the high reactive conformer of glucose, J. Am. Chem. Soc., 126 (2004) 12374-12385. 

The influence of the size and configuration of various cyclic vinyl carriers (Scheme 6.26) on the stereoselectivity of cycloaddition was studied, and included epoxides, (3-lactams, dioxaborolanes, and dioxans (22). Although the anti preference was maintained in all cases, the conformation of the carrier ring must also be taken into account in order to rationalize the stereoselections observed. The highest diastereomeric ratio was observed with the vinyl-tetrahydrofuran derived from glucose, where the conformational mobility of the carrier ring is substantially locked by an acetonide clamp and one face of the C=C bond is effectively shielded (22,165,215). 

---