5.4. Mutarotation

Saccharides may undergo additional chemical reactions, either in the lab (see Section 5.8) or in biological systems. Some of these chemical reactions affect the functional groups of the saccharide. As long as no reaction has affected the hemiacetal (or the carbonyl and relevant alcohol in the open form) then the saccharide is able to interconvert between forms; provided the saccharide still has a hemiacetal it can change forms.

One of the interconversions switches between the α- and β-anomers. This process is called mutarotation. During mutarotation the cyclic form opens, the bond to the carbonyl rotates, and then the ring re-forms (Scheme 5.6). This switches which anomer the molecule is in (full mechanism omitted for clarity).

Scheme 5.6 – Simplified Mutarotation of D-Glucopyranose.

Mutarotation occurs spontaneously, but relatively slowly, in water. However, the process can be catalyzed by either acid or base (Scheme 5.7). Many different acids or bases may be used. Because this is occurring in a complex biological system (with a large variety of available acids/bases) a generic acid/base is often shown to indicate this.

Scheme 5.7 – Acid- and Base-Catalyzed Mechanisms for Mutarotation of D-Glucopyranose.

5.4.1. Monosaccharides in Equilibrium

The other interconversion switches between the 6-membered ring (pyranose) form and the 5-membered ring (furanose) form. This does not occur for all saccharides, only those capable of adopting both 5- and 6-membered rings. During this process the cyclic form re-opens, a different bond rotates, and then the ring re-forms (Scheme 5.8). This switches which constitutional isomer the molecule is in (full mechanism omitted for clarity).

Scheme 5.8 – Simplified Interconversion of β-D-Glucopyranose and β-D-Glucofuranose.

Like mutarotation, this occurs spontaneously, but relatively slowly, in water. Again, the process can be catalyzed by either acid or base (Scheme 5.9). Many different acids or bases may be used. Because this is occurring in a complex biological system (with a large variety of available acids/bases) a generic acid/base is often shown to indicate this. The acid-catalyzed mechanism is functionally identical to mutarotation. The base-catalyzed mechanism is as well, but with an additional acid-base step to change which oxygen acts as the nucleophile during recyclization.

Scheme 5.9 – Acid- and Base-Catalyzed Mechanisms for Interconversion of β-D-Glucopyranose and β-D-Glucofuranose.

Both interconversions proceed through the same intermediate, the open form. Viewed differently, the open form is interconverting into each of the different isomers depending on which cyclization of which conformation occurs (Scheme 5.10).

Scheme 5.10 – Interconversions of D-Glucose to α/β-Anomers of Furanose and Pyranose Forms.

The alpha-anomer (α-anomer) and beta-anomer (β-anomer) are diastereomers. This is true in both the 5-membered (furanose) form and the 6-membered (pyranose) form. Recall that diastereomers have different physical and chemical properties; the anomers will have different energies/stabilities from each other. At equilibrium there will be different amounts of each anomer. The 5-membered ring (furanose), 6-membered ring (pyranose), and open form are constitutional isomers. Constitutional isomers are different molecules and have different physical and chemical properties; the different forms will have different energies/stabilities from each other. At equilibrium there will be different amounts of each form. The overall result is that many monosaccharides exist as an interconverting mixture of several different forms. These different forms will have different relative amounts at equilibrium (Scheme 5.11).

Scheme 5.11 – Interconversions of D-Fructose to α/β-Anomers of Furanose and Pyranose Forms with Relative Amounts at Equilibrium.

Each monosaccharide is distinct: the hexoses are different diastereomers of the same molecule, and are a different molecule than the tri-/tetra-/pent-oses; the pentoses are different diastereomers of the same molecule, and are a different molecule than the tri-/tetra-/hex-oses; etc. As a result, the exact ratio of each form at equilibrium will vary depending on the monosaccharide itself. For example, D-fructose and D-glucose have very different ratios of their different forms (Scheme 5.12).

Scheme 5.12 – Interconversions of D-Fructose and D-Glucose to α/β-Anomers of Furanose and Pyranose Forms with Relative Amounts at Equilibrium.

Knowing the exact relative amounts of each form of each saccharide is not straightforward; it is not possible to simply examine the structures and intuit the relative amounts of each. For the twenty-three common saccharides a large amount of experimental data has been gathered. The ratios of each form at equilibrium are known, very accurately, empirically. At an introductory level it is not required to memorize these values, it is important only to understand that the relative amounts of each form will vary and that the information is available.

Depending on the exact structure of the molecule determining these ratios experimentally may be simple or very challenging. For many synthetic saccharides not enough data exists to accurately determine the equilibrium ratios of the different forms. This information is typically gathered only if it is relevant for the application the synthetic saccharide is needed for.