Monosaccharides Are Aldehydes or Ketones with Multiple Hydroxyl Groups

Carbohydrates in food are important sources of energy. Starch, found in plant-derived food such as pasta, consists of
chains of linked glucose molecules. These chains are broken down into individual glucose molecules for eventual use in
generation of ATP and building blocks for other molecules. [(Left) Superstock.]
I. The Molecular Design of Life
11. Carbohydrates
11.1. Monosaccharides Are Aldehydes or Ketones with Multiple Hydroxyl Groups
Monosaccharides, the simplest carbohydrates, are aldehydes or ketones that have two or more hydroxyl groups; the
empirical formula of many is (C-H2O)n, literally a "carbon hydrate." Monosaccharides are important fuel molecules as
well as building blocks for nucleic acids. The smallest monosaccharides, for which n = 3, are dihydroxyacetone and dand l-glyceraldehyde.
They are referred to as trioses (tri- for 3). Dihydroxyacetone is called a ketose because it contains a keto group, whereas
glyceraldehyde is called an aldose because it contains an aldehyde group. Glyceraldehyde has a single asymmetric
carbon and, thus, there are two stereoisomers of this sugar. d-Glyceraldehyde and l-glyceraldehyde are enantiomers, or
mirror images of each other. As mentioned in Chapter 3, the prefixes d and l designate the absolute configuration.
Monosaccharides and other sugars will often be represented in this book by Fischer projections (Figure 11.1). Recall
that, in a Fischer projection of a molecule, atoms joined to an asymmetric carbon atom by horizontal bonds are in front
of the plane of the page, and those joined by vertical bonds are behind (see the Appendix in Chapter 1). Fischer
projections are useful for depicting carbohydrate structures because they provide clear and simple views of the
stereochemistry at each carbon center.
Simple monosaccharides with four, five, six, and seven carbon atoms are called tetroses, pentoses, hexoses, and
heptoses, respectively. Because these molecules have multiple asymmetric carbons, they exist as diastereoisomers,
isomers that are not mirror images of each other, as well as enantiomers. In regard to these monosaccharides, the
symbols d and l designate the absolute configuration of the asymmetric carbon farthest from the aldehyde or keto group.
Figure 11.2 shows the common d-aldose sugars. d-Ribose, the carbohydrate component of RNA, is a five-carbon aldose.
d-Glucose, d-mannose, and d-galactose are abundant six-carbon aldoses. Note that d-glucose and d-mannose differ in
configuration only at C-2. Sugars differing in configuration at a single asymmetric center are called epimers. Thus, dglucose and d-mannose are epimeric at C-2; d-glucose and d-galactose are epimeric at C-4.
Dihydroxyacetone is the simplest ketose. The stereochemical relation between d-ketoses containing as many as six
carbon atoms are shown in Figure 11.3. Note that ketoses have one fewer asymmetric center than do aldoses with the
same number of carbons. d-Fructose is the most abundant ketohexose.
11.1.1. Pentoses and Hexoses Cyclize to Form Furanose and Pyranose Rings
The predominant forms of ribose, glucose, fructose, and many other sugars in solution are not open chains. Rather, the
open-chain forms of these sugars cyclize into rings. In general, an aldehyde can react with an alcohol to form a
hemiacetal.
For an aldohexose such as glucose, the C-1 aldehyde in the open-chain form of glucose reacts with the C-5 hydroxyl
group to form an intramolecular hemiacetal. The resulting cyclic hemiacetal, a six-membered ring, is called pyranose
because of its similarity to pyran (Figure 11.4). Similarly, a ketone can react with an alcohol to form a hemiketal.
The C-2 keto group in the open-chain form of a ketohexose, such as fructose, can form an intramolecular hemiketal by
reacting with either the C-6 hydroxyl group to form a six-membered cyclic hemiketal or the C-5 hydroxyl group to form
a five-membered cyclic hemiketal (Figure 11.5). The five-membered ring is called a furanose because of its similarity to
furan.
The depictions of glucopyranose and fructofuranose shown in Figures 11.4 and 11.5 are Haworth projections. In such
projections, the carbon atoms in the ring are not explicitly shown. The approximate plane of the ring is perpendicular to
the plane of the paper, with the heavy line on the ring projecting toward the reader. Like Fischer projections, Haworth
projections allow easy depiction of the stereochemistry of sugars. We will return to a more structurally realistic view of
the conformations of cyclic monosaccharides shortly.
An additional asymmetric center is created when a cyclic hemiacetal is formed. In glucose, C-1, the carbonyl carbon
atom in the open-chain form, becomes an asymmetric center. Thus, two ring structures can be formed: α -dglucopyranose and β -d-glucopyranose (see Figure 11.4). For d sugars drawn as Haworth projections, the designation α
means that the hydroxyl group attached to C-1 is below the plane of the ring; β means that it is above the plane of the
ring. The C-1 carbon atom is called the anomeric carbon atom, and the α and β forms are called anomers. An
equilibrium mixture of glucose contains approximately one-third α anomer, two-thirds β anomer, and <1% of the openchain form.
The same nomenclature applies to the furanose ring form of fructose, except that α and β refer to the hydroxyl groups
attached to C-2, the anomeric carbon atom (see Figure 11.5). Fructose forms both pyranose and furanose rings. The
pyranose form predominates in fructose free in solution, and the furanose form predominates in many fructose
derivatives (Figure 11.6). Pentoses such as d-ribose and 2-deoxy-d-ribose form furanose rings, as we have seen in the
structure of these units in RNA and DNA.
11.1.2. Conformation of Pyranose and Furanose Rings
The six-membered pyranose ring is not planar, because of the tetrahedral geometry of its saturated carbon atoms.
Instead, pyranose rings adopt two classes of conformations, termed chair and boat because of the resemblance to these
objects (Figure 11.7). In the chair form, the substituents on the ring carbon atoms have two orientations: axial and
equatorial. Axial bonds are nearly perpendicular to the average plane of the ring, whereas equatorial bonds are nearly
parallel to this plane. Axial substituents sterically hinder each other if they emerge on the same side of the ring (e.g., 1,3diaxial groups). In contrast, equatorial substituents are less crowded. The chair form of β - d -glucopyranose
predominates because all axial positions are occupied by hydrogen atoms. The bulkier -OH and -CH2OH groups emerge
at the less-hindered periphery. The boat form of glucose is disfavored because it is quite sterically hindered.
Furanose rings, like pyranose rings, are not planar. They can be puckered so that four atoms are nearly coplanar and the
fifth is about 0.5 Å away from this plane (Figure 11.8). This conformation is called an envelope form because the
structure resembles an opened envelope with the back flap raised. In the ribose moiety of most biomolecules, either C-2
or C-3 is out of the plane on the same side as C-5. These conformations are called C2-endo and C3-endo, respectively.
11.1.3. Monosaccharides Are Joined to Alcohols and Amines Through Glycosidic Bonds
Monosaccharides can be modified by reaction with alcohols and amines to form adducts. For example, d-glucose will
react with methanol in an acid-catalyzed process: the anomeric carbon atom reacts with the hydroxyl group of methanol
to form two products, methyl α -d-glucopyranoside and methyl β -d-glucopyranoside. These two glucopyranosides differ
in the configuration at the anomeric carbon atom. The new bond formed between the anomeric carbon atom of glucose
and the hydroxyl oxygen atom of methanol is called a glycosidic bond specifically, an O-glycosidic bond. The
anomeric carbon atom of a sugar can be linked to the nitrogen atom of an amine to form an N-glycosidic bond.
Indeed, we have previously encountered such reaction products; nu-cleosides are adducts between sugars such as ribose
and amines such as adenine (Section 5.1.1). Some other important modified sugars are shown in Figure 11.9.
Compounds such as methyl glucopyranoside show differences in reactivity from that of the parent monosaccharide. For
example, unmodified glucose reacts with oxidizing agents such as cupric ion (Cu2+) because the open-chain form has a
free aldehyde group that is readily oxidized.
Glycosides such as methyl glucopyranoside do not react, because they are not readily interconverted with a form that
includes a free aldehyde group. Solutions of cupric ion (known as Fehling's solution) provide a simple test for sugars
such as glucose. Sugars that react are called reducing sugars; those that do not are called nonreducing sugars.
I. The Molecular Design of Life
11. Carbohydrates
11.1. Monosaccharides Are Aldehydes or Ketones with Multiple Hydroxyl Groups
Figure 11.1. Fischer Projections of Trioses. The top structure reveals the stereochemical relations assumed for Fischer
projections.
I. The Molecular Design of Life
11. Carbohydrates
11.1. Monosaccharides Are Aldehydes or Ketones with Multiple Hydroxyl Groups
Figure 11.2. d-Aldoses containing three, four, five, and six carbon atoms. d-Aldoses contain an aldehyde group
(shown in blue) and have the absolute configuration of d-glyceraldehyde at the asymmetric center (shown in red) farthest
from the aldehyde group. The numbers indicate the standard designations for each carbon atom.
I. The Molecular Design of Life
11. Carbohydrates
11.1. Monosaccharides Are Aldehydes or Ketones with Multiple Hydroxyl Groups
Figure 11.3. d -Ketoses containing three- four, five, and six carbon atoms. The keto group is shown in blue. The
asymmetric center farthest from the keto group, which determines the d designation, is shown in red.
I. The Molecular Design of Life
11. Carbohydrates
11.1. Monosaccharides Are Aldehydes or Ketones with Multiple Hydroxyl Groups
Figure 11.4. Pyranose Formation. The open-chain form of glucose cyclizes when the C-5 hydroxyl group attacks the
oxygen atom of the C-1 aldehyde group to form an intramolecular hemiacetal. Two anomeric forms, designated α and β ,
can result.
I. The Molecular Design of Life
11. Carbohydrates
11.1. Monosaccharides Are Aldehydes or Ketones with Multiple Hydroxyl Groups
Figure 11.5. Furanose Formation. The open-chain form of fructose cyclizes to a five-membered ring when the C-5
hydroxyl group attacks the C-2 ketone to form an intramolecular hemiketal. Two anomers are possible, but only the α
anomer is shown.
I. The Molecular Design of Life
11. Carbohydrates
11.1. Monosaccharides Are Aldehydes or Ketones with Multiple Hydroxyl Groups
Figure 11.6. Ring Structures of Fructose. Fructose can form both five-membered furanose and six-membered pyranose
rings. In each case, both α and β anomers are possible.
I. The Molecular Design of Life
11. Carbohydrates
11.1. Monosaccharides Are Aldehydes or Ketones with Multiple Hydroxyl Groups
Figure 11.7. Chair and Boat Forms of β - d -glucopyranose. The chair form is more stable because of less steric
hindrance as the axial positions are occupied by hydrogen atoms.