Mutarotation: The α,β Sugars Interconversion

Mutarotation, discovered by Augustin Pierre Dubrunfaut in 1844, is the interconversion of alpha(α) and beta(β) anomeric forms of cyclic sugars. This interconversion is the change in the optical rotation property which develops over time. Mutarotation is the effect of ring-chain tautomerism, exhibited by sugars with hemiacetal linkages, that undergo interconversion of alpha(α) isomers to beta(β) ones along with the straight-chain form.

The alpha and beta anomeric isomers are in fact not in direct equilibrium with each other, but both are in direct equilibrium with the open-chain form. It means that there is an indirect equilibrium between alpha and beta forms of saccharides. The concept of mutarotation can be well understood by relating it to thermodynamics.

When a body is in thermal equilibrium with a second body, which is further, in thermal equilibrium with a third body, the first and third bodies are also in thermal equilibrium. This law is termed as Zeroth Law of thermodynamics. This is the reason why alpha anomer is in equilibrium with beta anomer.

Sugars that are capable of mutarotation are called reducing sugars as they react with oxidizing agents. This capability of mutarotation is governed by the presence of a free hemiacetal group (or a hemiketal group). Once the hemiacetal group is not stable and converts to acetal, that saccharide containing compound is no longer capable of mutarotation and is now categorized as a non-reducing sugar.

Mutarotation ↔ Reducing sugars

No mutarotation ↔ Non-reducing sugars

There are many examples of compounds that exhibit mutarotation. Some examples of such reducing sugars are:

Glucose
Fructose
Galactose
Xylose
Maltose
Lactose
Arabinose
Mannose, etc.

Some compounds that do not show mutarotation and are non-reducing sugars are:

Sucrose
Glycosides
Trehalose
Raffinose
Stachyose
Verbascose, etc.

Explanations of mutarotations in reducing and no mutarotation in non-reducing sugars are given below.

Mutarotation in Glucose (α and β-D Glucose)

The most abundant monosaccharide in the world is D-glucose, which exists as alpha (α) and beta (β)-D glucose. In an aqueous solution of glucose, the alpha(α) and beta(β) forms co-exist. For an equilibrium to establish between these anomeric forms, the α-D glucose having an optical rotation value of +112.2°, interconverts to the β-D glucose with an optical rotation value of +18.7° and vice versa. This gives rise to an overall optical rotation value of +52.7°, i.e. the equilibrium optical rotation value for D-glucose. When a polarimeter shows an exact value of +52.7°, it indicates the complete establishment of equilibrium between alpha and beta anomeric forms of glucose.

Mutarotation in glucose leads to an equilibrium mixture with 37% of the alpha(α)-D glucose and 63% of the beta(β)-D glucose. Acyclic (open chain) aldehyde form of glucose only exists in trace amounts.

Mutarotation in Fructose (α and β-D Fructose)

Fructose is the sweetest sugar of all, also called ‘levulose’ and ‘fruit sugar’ is usually found in honey, corn syrup, sweet fruits, etc. Unlike glucose, it forms five-membered ringed cyclic hemiacetals (in case of pyranoses) with anomeric carbon at C-2. Furthermore, fructose belongs to the ketoses while glucose is from the aldoses family. The aldose and ketose sugars differ in their functional group identification.

D-fructose is one of the sugars that have complex mutarotation like D-arabinose and D-galactose, etc. Such sugars have more than two tautomers (ring-chain tautomers) at equilibrium conditions. The tautomers of fructose include α-D fructopyranose, α-D fructofuranose, β-D fructopyranose, and β-D fructofuranose.

The mutarotation of fructose can simply be explained by the interconversion relation between the ketone acyclic form, the α-D fructose, and β-D fructose.

Just like glucose, the alpha and beta forms of D-fructose are not directly interconvertible, they pass through an open-chain form (ketone in this case).

Related topics

Mutarotation in Galactose (α and β-D Galactose)

Galactose is one of the sugars having pseudo-first-order kinetics for mutarotation reactions. They are expected to have two general tautomeric forms i.e. α-D galactose and β-D galactose. Some recent studies suggest that it also contains a third tautomer named γ-D galactose, however, no such evidence has been spotted in solutions of D-galactose in deuterium oxide.

Galactose is a sugar, similar to glucose, with a difference at the C-4 configuration. This C-4 has a hydroxyl group that has an equatorial position in α-D galactopyranose and axial position in β-D glucopyranose form.

D-galactose is one of the monomers of lactose, other than D-glucose. It is also the monomer in sucralose (the newest artificial sweetener). It involves four tautomeric forms including, α-D galactopyranose, β-D galactopyranose, α-D galactofuranose, and β-D galactofuranose.

Mutarotation in Maltose (α and β Maltose)

Maltose, a disaccharide of two α-D glucose monomers, is formed by the alpha(α) glycoside linkage. Alpha glycoside linkage, also called a 1,4 α-glycosidic bond forms between two monomers and makes the anomeric carbon of one α-D glucose, get covered, while that of the second one is still available for mutarotation. It means that there are two maltose structures i.e. α-maltose and β-maltose.

Maltose is a hemiacetal containing carbohydrate, which enables mutarotation and its reactions with oxidizing agents. As a consequence, maltose becomes a reducing sugar.

Mutarotation in Lactose (α and β Lactose)

Lactose is also a disaccharide, usually found in milk. It is formed by the 1,4-β glycosidic bond between galactose and a glucose molecule. This glycosidic linkage is formed between the anomeric carbon of galactose and the C-4 carbon of glucose, leaving the anomeric carbon of glucose (C-1) unattended. Such carbon makes alpha to beta interconversion possible, thus making lactose, able of mutarotation and as a consequence, it exists as α-lactose and β-lactose.

Mutarotation: The α , β maltose lactose sugars, Interconversion for lactose

Lactose is capable of mutarotation and it reacts with oxidizing agents which makes it a reducing sugar. Like maltose, it also contains a hemiacetal group which is responsible for this property of mutarotation.

No Mutarotation in Sucrose

Sucrose, the table sugar, is the most common disaccharide sugar found in nature. It is formed by one glucose and one fructose unit as monomers.

Sucrose is significantly different from maltose and lactose because of its unique α-glycosidic bond. The anomeric carbon of glucose monomer (C-1) is joined to the anomeric carbon of fructose monomer (C-2), making sucrose an acetal molecule. This absence of hemiacetal and hemiketal structures makes sucrose unable to show mutarotation leading to the non-reducing nature of sucrose.

Sucrose is also known as ‘invert sugar’. The optical rotation value of +66.5° according to polarimetry. Upon hydrolysis, it yields an equimolar solution of glucose and fructose having an overall optical rotation value of -22.0°. This turn-about of the optical property of sucrose makes it an inverting sugar.

No Mutarotation in Glycosides

Glycosides are formed by the treatment of monosaccharides with alcoholic HCl, to convert the hemiacetals to acetals. In other words, glycosides are acetals with alkoxy (-OR) functionality with the anomeric carbon. These glycosides can be converted back to hemiacetals by acidified hydrolysis.

Glycosides are acetals, due to which, they are unable to show mutarotation properties.

No Mutarotation in Trehalose

Trehalose is the blood sugar in the insect world usually found in fungi (mushrooms), bacterial spores, resurrection plants (Selaginella), and many insects having a habitat of large temperature variations.

Trehalose is a disaccharide sugar, similar to sucrose, with two α-D glucose monomers. As the anomeric centers of D-glucose (C-1) are occupied in both monomers, trehalose lacks the property of mutarotation just like sucrose.

No mutarotation in trehalose

Key Takeaway(s)

Mutarotation is a process by which one anomer of a monosaccharide converts to an equilibrium mixture or equilibrates to a solution of both anomers of the same monosaccharide.

There are some disaccharides that show mutarotation as well, like maltose, lactose, etc, for which they are called reducing sugars.
Sugars like sucrose, trehalose, and glycosides do not show mutarotation, which is why they are called non-reducing sugars.

Concepts Berg

Is mutarotation only for glucose?

Mutarotation involves all sugars having an anomeric center as hemiacetal or hemiketal, like glucose, fructose, galactose, maltose, lactose, etc.

What does equilibrium between anomers mean?

Mutarotation makes two anomers of the same saccharide co-exist in equimolar concentrations, which is termed as the equilibrium between anomers.

What is a non-reducing sugar and why don’t they show mutarotation?

Non-reducing sugars are saccharides that possess acetal structures. This lack of hemiacetal or hemiketal makes them unable to show mutarotation.

How does mutarotation occur?

Mutarotation occurs when a configuration change is experienced between alpha and beta anomers of the same sugar molecules.

What is meant by the mutarotation of glucose?

Mutarotation of glucose is the interconvertibility of alpha and beta D glucose.

What is the cause of mutarotation of glucose?

Mutarotation of glucose is due to the hemiacetal identity present on anomeric carbon present on C-1 of D-glucose.

Why does D glucose show the phenomenon of mutarotation?

D-glucose shows the mutarotation property based on anomeric carbon having a hemiacetal identity. The same goes for fructose, with hemiketal identity.

What are some examples of mutarotation?

Mutarotation is observed in monosaccharide molecules like,

Glucose
Fructose
Galactose
Xylose
Arabinose
Mannose, etc.

Some disaccharides also show mutarotation like,

Maltose
Lactose, etc.

What is the inversion of sugars?

Inversion of sugars is the property of inverted optical properties upon hydrolysis. Sucrose shows opposite optical properties in hydrolyzed and non-hydrolyzed, for which it is referred to as ‘invert sugar’.

How many chiral centers does glucose have?

There are four chiral centers of glucose.

How do maltose and cellobiose differ?

Maltose and cellulose, both are disaccharides of D-glucose. The main difference between maltose and cellulose is that maltose has a C-1 linkage for alpha position, while cellulose has the same with beta position.

How to increase the rate of mutarotation of glucose?

The mutarotation of glucose can be significantly increased by the continuous removal of product anomer. Moreover, advanced studies suggest that an increase in pressure also serves the purpose.

Mutarotation in cyclic carbohydrates

Mutarotation is shown by only cyclic carbohydrates. Although they essentially involve a third structure of acyclic aldehydes or ketones.

Mutarotation in biochemistry

Mutarotation is the property of chemical biology, involving the interconversion in the optical property of molecules.

Reference books

Organic Chemistry (Fourth edition), Paula Yurkanis Bruice, University of California, Santa Barbara
Organic Chemistry (4th edition), Francis A. Carey, University of Virginia
Organic Chemistry (Third Edition), Janice Gorzynski Smith, University of Hawai’i at Manoa

Reference links