2.6: Cyclic Structures of Monosaccharides

Objectives

After completing this section, you should be able to

1. determine whether a given monosaccharide will exist as a pyranose or furanose.
2. draw the cyclic pyranose form of a monosaccharide, given its Fischer projection.
3. draw the Fischer projection of a monosaccharide, given its cyclic pyranose form.
4. draw, from memory, the cyclic pyranose form of D‑glucose.
5. determine whether a given cyclic pyranose form represents the D or L form of the monosaccharide concerned.
6. describe the phenomenon known as mutarotation.
7. explain, through the use of chemical equations, exactly what happens at the molecular level during the mutarotation process.

Key Terms

Make certain that you can define, and use in context, the key terms below.

• alpha anomer
• anomer
• anomeric centre
• beta anomer
• furanose
• mutarotation
• pyranose

Study Notes

If necessary, before you attempt to study this section, review the formation of hemiacetals discussed in Section 19.10.

Cyclic hemiacetal formation

In organic chemistry, we described the reaction between carbonyl compounds and alcohol to form hemiacetal and hemiketal respectively, 

Image by Kupirijo at English Wikipedia, CC BY-SA 3.0, via Wikimedia Commons

In a monosaccharide, the carbonyl (C=O) and alcohol group (OH)  exist within the same molecule, so they can react forming a cyclic hemiacetal (or hemiketal, in the case of ketoses). The resulting structure will be an intramolecular cyclic hemiacetal. The carbonyl carbon (C1) becomes sp3 hybridized, with four different groups attached to it. This carbon is now chiral, and it is called the anomeric carbon. Five and six-membered rings are favored over other ring sizes because of their low angle and eclipsing strain. This means that the aldehyde group in aldohexoses react with carbon 5 to format a six-membered ring, while in the case of aldopentoses,  the aldehyde group in aldohexoses react with carbon 4 to format a five-membered ring. These are the most important examples of cyclic hemiacetal formation in monosaccharides. Cyclic structures of this kind are termed furanose (five-membered) or pyranose (six-membered), reflecting the ring size relationship to the common heterocyclic compounds furan and pyran shown on the right.

For example, ribose, an important aldopentose, commonly adopts a furanose structure, as shown in the following illustration. By convention for the D-family, the five-membered furanose ring is drawn in an edgewise projection with the ring oxygen positioned away from the viewer. The anomeric carbon atom (colored orange here) is placed on the right.

When a straight-chain monosaccharide, such as any of the structures shown in ribose, forms a cyclic structure, the carbonyl oxygen atom may be pushed either up or down, giving rise to two stereoisomers. The structure shown on the left side of Figure 2, with the OH group on the first carbon atom projected downward, represent what is called the alpha (α) form. The structures on the right side, with the OH group on the first carbon atom pointed upward, is the beta (β) form. These two stereoisomers of a cyclic monosaccharide are known as anomers; they differ in structure around the anomeric carbon—that is, the carbon atom that was the carbonyl carbon atom in the straight-chain form.

Commonly,  the cyclic forms of sugars are depicted using a convention first suggested by Walter N. Haworth, an English chemist.  In a Haworth projection or formula, the molecules are drawn as planar hexagons with a darkened edge representing the side facing toward the viewer. The anomeric carbon is placed on the right with the ring oxygen to the back of the edgewise view. In the D-family, the -CH₂OH always points up. 
The structure is simplified to show only the functional groups attached to the carbon atoms. Any group written to the right in a Fischer projection appears below the plane of the ring in a Haworth projection, and any group written to the left in a Fischer projection appears above the plane in a Haworth projection.  

A similar intramolecular reaction occurs with the glucose molecule, resulting in two possible anomers: α-D-glucopyranose and β-D-glucopyranose:

 

Figure 1: Cyclization of D-Glucose. D-Glucose can be represented with a Fischer projection (a) or three dimensionally (b). By reacting the OH group on the fifth carbon atom with the aldehyde group, the cyclic monosaccharide  α-D-glucopyranose (c) is produced. In β-D-glucopyranose, the OH group on the anomeric carbon points up.

These Haworth formulas are convenient for displaying stereochemical relationships, but do not represent the true shape of the molecules. We know that these molecules are actually puckered in a fashion we call a chair conformation. Examples of four typical pyranose structures are shown below, both as Haworth projections and as the more representative chair conformers. The anomeric carbons are colored red.

In order to interconvert between Fisher projection (for open-chain structures), Haworth and Chair conformations (for cyclic structures), this table can be very useful: 

 

Fischer Projection	Haworth Projection	Chair conformation	Anomer
Right	Down	Axial	𝛂
Left	Up	Equatorial	𝛃

 

 

Anomers of Simple Sugars: Mutarotation of Glucose

It is possible to obtain a sample of crystalline glucose in which all the molecules have the α structure or all have the β structure. The α form melts at 146°C and has a specific rotation of +112°, while the β form melts at 150°C and has a specific rotation of +18.7°. When the sample is dissolved in water, however, a mixture is soon produced containing both anomers as well as the straight-chain form, in dynamic equilibrium (part (a) of Figure 2). You can start with a pure crystalline sample of glucose consisting entirely of either anomer, but as soon as the molecules dissolve in water, they open to form the carbonyl group and then reclose to form either the α or the β anomer. The opening and closing repeats continuously in an ongoing interconversion between anomeric forms and is referred to as mutarotation (Latin mutare, meaning “to change”). At equilibrium, the mixture consists of about 36% α-D-glucose, 64% β-D-glucose, and less than 0.02% of the open-chain aldehyde form. The observed rotation of this solution is +52.7°.

 

Figure 2: Monosaccharides. In an aqueous solution, monosaccharides exist as an equilibrium mixture of three forms. The interconversion between the forms is known as mutarotation, which is shown for D-glucose (a) and D-fructose (b).

 

Even though only a small percentage of the molecules are in the open-chain aldehyde form at any time, the solution will nevertheless exhibit the characteristic reactions of an aldehyde. As the small amount of free aldehyde is used up in a reaction, there is a shift in the equilibrium to yield more aldehyde. Thus, all the molecules may eventually react, even though very little free aldehyde is present at a time. This is because the mutarotation reaction is an equilibrium reaction, so removing any of the molecules involved in this equilibrium would make the equilibrium shift in that direction (le Chatelier's princriple)  

 

The difference between the α and the β forms of sugars may seem trivial, but such structural differences are often crucial in biochemical reactions. This explains why we can get energy from the starch in potatoes and other plants but not from cellulose, even though both starch and cellulose are polysaccharides composed of glucose molecules linked together.

Summary

Monosaccharides that contain five or more carbons atoms form cyclic structures in aqueous solution. Two cyclic stereoisomers can form from each straight-chain monosaccharide; these are known as anomers. In an aqueous solution, an equilibrium mixture forms between the two anomers and the straight-chain structure of a monosaccharide in a process known as mutarotation.

Exercises

1. Draw the cyclic structure for β-D-glucose. Identify the anomeric carbon.

2. Given that the aldohexose D-mannose differs from D-glucose only in the configuration at the second carbon atom, draw the cyclic structure for α-D-mannose.

Answers

1. 

 

2.

Contributors and Attributions

• Dr. Dietmar Kennepohl FCIC (Professor of Chemistry, Athabasca University)

• Prof. Steven Farmer (Sonoma State University)

• William Reusch, Professor Emeritus (Michigan State U.), Virtual Textbook of Organic Chemistry

• The Basics of General, Organic, and Biological Chemistry by David W. Ball, John W. Hill, and Rhonda J. Scott.