25.5 • Cyclic Structures of Monosaccharides: Anomers
We said in Section 19.10 that aldehydes and ketones undergo a rapid and reversible nucleophilic addition reaction with alcohols to form hemiacetals.
If the carbonyl and the hydroxyl group are in the same molecule, an intramolecular nucleophilic addition can take place, leading to the formation of a cyclic hemiacetal. Five- and six-membered cyclic hemiacetals are relatively strain-free and particularly stable, and many carbohydrates therefore exist in an equilibrium between open-chain and cyclic forms. Glucose, for instance, exists in aqueous solution primarily in the six-membered pyranose form resulting from intramolecular nucleophilic addition of the –OH group at C5 to the C1 carbonyl group (Figure 25.5). The name pyranose is derived from pyran, the name of the unsaturated six-membered cyclic ether.
Like cyclohexane rings (Section 4.6), pyranose rings have a chairlike geometry with axial and equatorial substituents. By convention, the rings are usually drawn by placing the hemiacetal oxygen atom at the right rear, as shown in Figure 25.5. Note that an –OH group on the right in a Fischer projection is on the bottom face of the pyranose ring, and an –OH group on the left in a Fischer projection is on the top face of the ring. For D sugars, the terminal –CH2OH group is on the top of the ring, whereas for L sugars, the –CH2OH group is on the bottom.
When an open-chain monosaccharide cyclizes to a pyranose form, a new chirality center is generated at the former carbonyl carbon and two diastereomers, called anomers, are produced. The hemiacetal carbon atom is referred to as the anomeric center. For example, glucose cyclizes reversibly in aqueous solution to a 37 : 63 mixture of two anomers (Figure 25.5). The compound with its newly generated –OH group at C1 cis to the –OH at the lowest chirality center in a Fischer projection is called the α anomer; its full name is α-D-glucopyranose. The compound with its newly generated –OH group trans to the –OH at the lowest chirality center is called the β anomer; its full name is β-D-glucopyranose. Note that in β-D-glucopyranose, all the substituents on the ring are equatorial. Thus, β-D-glucopyranose is the least sterically crowded and most stable of the eight D aldohexoses.
Some monosaccharides also exist in a five-membered cyclic hemiacetal form called a furanose. D-Fructose, for instance, exists in water solution as 68% β-pyranose, 2.7% α-pyranose, 0.5% open-chain, 22.4% β-furanose, and 6.2% α-furanose. The pyranose form results from addition of the –OH at C6 to the carbonyl group, while the furanose form results from addition of the –OH at C5 to the carbonyl group (Figure 25.6).
Both anomers of D-glucopyranose can be crystallized and purified. Pure α-D-glucopyranose has a melting point of 146 °C and a specific rotation [α]D = +112.2; pure β-D-glucopyranose has a melting point of 148 to 155 °C and a specific rotation [α]D = +18.7. When a sample of either pure anomer is dissolved in water, however, its optical rotation slowly changes until it reaches a constant value of +52.6. That is, the specific rotation of the α-anomer solution decreases from +112.2 to +52.6, and the specific rotation of the β-anomer solution increases from +18.7 to +52.6. Called mutarotation, this change in optical rotation is due to the slow interconversion of the pure anomers to give the same 37 : 63 equilibrium mixture.
Mutarotation occurs by a reversible ring-opening of each anomer to the open-chain aldehyde, followed by reclosure. Although the equilibration is slow at neutral pH, it is catalyzed by both acid and base.
Drawing the Chair Conformation of an Aldohexose
D-Mannose differs from D-glucose in its stereochemistry at C2. Draw D-mannose in its chairlike pyranose form.
StrategyFirst draw a Fischer projection of D-mannose. Then lay it on its side, and curl it around so that the –CHO group (C1) is on the right front and the –CH2OH group (C6) is toward the left rear. Now, connect the –OH at C5 to the C1 carbonyl group to form the pyranose ring. In drawing the chair form, raise the leftmost carbon (C4) up and drop the rightmost carbon (C1) down.
Drawing the Chair Conformation of a Pyranose
Draw β-L-glucopyranose in its more stable chair conformation.