Carey - Organic Chemistry - chapt25

Carey - Organic Chemistry - chapt25

(Parte 1 de 6)


The major classes of organic compounds common to living systems are lipids, proteins, nucleic acids,and carbohydrates.Carbohydrates are very familiar to us— we call many of them “sugars.” They make up a substantial portion of the food we eat and provide most of the energy that keeps the human engine running. Carbohydrates are structural components of the walls of plant cells and the wood of trees. Genetic information is stored and transferred by way of nucleic acids, specialized derivatives of carbohydrates, which we’l examine in more detail in Chapter 27. Historically, carbohydrates were once considered to be “hydrates of carbon” because their molecular formulas in many (but not all) cases correspond to Cn(H2O)m. It is more realistic to define a carbohydrate as a polyhydroxy aldehydeor polyhydroxy ketone,a point of view closer to structural reality and more suggestive of chemical reactivity.

This chapter is divided into two parts. The first, and major, portion is devoted to carbohydrate structure. You will see how the principles of stereochemistry and conformational analysis combine to aid our understanding of this complex subject. The remainder of the chapter describes chemical reactions of carbohydrates. Most of these reactions are simply extensions of what you have already learned concerning alcohols, aldehydes, ketones, and acetals.


The Latin word for “sugar”* is saccharum,and the derived term “saccharide” is the basis of a system of carbohydrate classification. Amonosaccharideis a simple carbohydrate, one that on attempted hydrolysis is not cleaved to smaller carbohydrates. Glucose

*“Sugar” is a combination of the Sanskrit words su(sweet) and gar(sand). Thus, its literal meaning is “sweet sand.”

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(C6H12O6), for example, is a monosaccharide. Adisaccharideon hydrolysis is cleaved to two monosaccharides, which may be the same or different. Sucrose—common table

sugar—is a disaccharide that yields one molecule of glucose and one of fructose on hydrolysis.

An oligosaccharide(oligosis a Greek word that in its plural form means “few”) yields 3–10 monosaccharide units on hydrolysis. Polysaccharidesare hydrolyzed to more than 10 monosaccharide units. Celluloseis a polysaccharide molecule that gives thousands of glucose molecules when completely hydrolyzed.

Over 200 different monosaccharides are known. They can be grouped according to the number of carbon atoms they contain and whether they are polyhydroxy aldehydes or polyhydroxy ketones. Monosaccharides that are polyhydroxy aldehydes are called aldoses;those that are polyhydroxy ketones are ketoses.Aldoses and ketoses are further classified according to the number of carbon atoms in the main chain. Table 25.1 lists the terms applied to monosaccharides having four to eight carbon atoms.


Stereochemistry is the key to understanding carbohydrate structure, a fact that was clearly appreciated by the German chemist Emil Fischer. The projection formulas used by Fischer to represent stereochemistry in chiral molecules are particularly well-suited to studying carbohydrates. Figure 25.1 illustrates their application to the enantiomers of glyceraldehyde(2,3-dihydroxypropanal), a fundamental molecule in carbohydrate stereochemistry. When the Fischer projection is oriented as shown in the figure, with the carbon chain vertical and the aldehyde carbon at the top, the C-2 hydroxyl group points to the right in ( )-glyceraldehyde and to the left in ( )-glyceraldehyde.

Techniques for determining the absolute configuration of chiral molecules were not developed until the 1950s, and so it was not possible for Fischer and his contemporaries to relate the sign of rotation of any substance to its absolute configuration. Asystem evolved based on the arbitrary assumption, later shown to be correct, that the enantiomers of glyceraldehyde have the signs of rotation and absolute configurations shown in Figure 25.1. Two stereochemical descriptors were defined: Dand L. The absolute configuration of ( )-glyceraldehyde, as depicted in the figure, was said to be Dand that of its enantiomer, ( )-glyceraldehyde, L. Compounds that had a spatial arrangement of substituents analogous to D-( )- and L-( )-glyceraldehyde were said to have the Dand L configurations, respectively.

TABLE 25.1Some Classes of Monosaccharides


Aldotetrose Aldopentose Aldohexose Aldoheptose Aldooctose


Ketotetrose Ketopentose Ketohexose Ketoheptose Ketooctose

Number of carbon atoms

Four Five Six Seven Eight

Adopting the enantiomers of glyceraldehyde as stereochemical reference compounds originated with proposals made in 1906 by M. A. Rosanoff, a chemist at New York University.

Fischer determined the structure of glucose in 1900 and won the Nobel Prize in chemistry in 1902.

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PROBLEM 25.1Identify each of the following as either D-or L-glyceraldehyde: (a) (b) (c)

SAMPLE SOLUTION(a) Redraw the Fischer projection so as to more clearly show the true spatial orientation of the groups. Next, reorient the molecule so that its relationship to the glyceraldehyde enantiomers in Figure 25.1 is apparent.

The structure is the same as that of ( )-glyceraldehyde in the figure. It is D- glyceraldehyde.

Fischer projections and D–Lnotation have proved to be so helpful in representing carbohydrate stereochemistry that the chemical and biochemical literature is replete with their use. To read that literature you need to be acquainted with these devices, as well as the more modern Cahn–Ingold–Prelog system.


Glyceraldehyde can be considered to be the simplest chiral carbohydrate. It is an aldotrioseand, since it contains one stereogenic center, exists in two stereoisomeric forms: the Dand Lenantiomers. Moving up the scale in complexity, next come the aldotetroses.Examination of their structures illustrates the application of the Fischer system to compounds that contain more than one stereogenic center.

The aldotetroses are the four stereoisomers of 2,3,4-trihydroxybutanal. Fischer projections are constructed by orienting the molecule in an eclipsed conformation with the aldehyde group at what will be the top. The four carbon atoms define the main chain of the Fischer projection and are arranged vertically. Horizontal bonds are directed outward, vertical bonds back.


CHO is equivalent to turn






974 CHAPTER TWENTY-FIVE Carbohydrates CHœO


CH2OH R-(+)-Glyceraldehyde


FIGURE 25.1 Threedimensional representations and Fischer projections of the enantiomers of glyceraldehyde.

Molecular models of the four stereoisomeric aldotetroses may be viewed on the CD that accompanies this text.

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The particular aldotetrose just shown is called D-erythrose.The prefix Dtells us that the configuration at the highest numbered stereogenic centeris analogous to that of D-( )- glyceraldehyde. Its mirror image is L-erythrose.

Relative to each other, both hydroxyl groups are on the same side in Fischer projections of the erythrose enantiomers. The remaining two stereoisomers have hydroxyl groups on opposite sides in their Fischer projection. They are diastereomers of D-and L-erythrose and are called D-and L-threose.The Dand Lprefixes again specify the configuration of the highest numbered stereogenic center. D-Threose and L-threose are enantiomers of each other:

PROBLEM 25.2Which aldotetrose is the structure shown? Is it D-erythrose, D-threose, L-erythrose, or L-threose? (Be careful! The conformation given is not the same as that used to generate a Fischer projection.)

Highest numbered stereogenic center has configuration analogous to that of D-glyceraldehyde





Highest numbered stereogenic center has configuration analogous to that of L-glyceraldehyde

Highest numbered stereogenic center has configuration analogous to that of D-glyceraldehyde





Highest numbered stereogenic center has configuration analogous to that of L-glyceraldehyde which iswritten asHC C



Fischer projection of a tetrose is equivalent to

Eclipsed conformation of a tetrose


For a first-person account of the development of systematic carbohydrate nomenclature see C. D. Hurd’s article in the December 1989 issue of the Journal of Chemical Education, p. 984–988.

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As shown for the aldotetroses, an aldose belongs to the Dor the Lseries according to the configuration of the stereogenic center farthest removed from the aldehyde function. Individual names, such as erythrose and threose, specify the particular arrangement of stereogenic centers within the molecule relative to each other. Optical activities cannot be determined directly from the Dand Lprefixes. As it turns out, both D-erythrose and D-threose are levorotatory, but D-glyceraldehyde is dextrorotatory.


Aldopentoses have three stereogenic centers. The eight stereoisomers are divided into a set of four D-aldopentoses and an enantiomeric set of four L-aldopentoses. The aldopentoses are named ribose, arabinose, xylose,and lyxose.Fischer projections of the D stereoisomers of the aldopentoses are given in Figure 25.2. Notice that all these diastereomers have the same configuration at C-4 and that this configuration is analogous to that of D-( )-glyceraldehyde.

PROBLEM 25.3L-( )-Arabinose is a naturally occurring Lsugar. It is obtained by acid hydrolysis of the polysaccharide present in mesquite gum. Write a Fischer projection for L-( )-arabinose.

Among the aldopentoses, D-ribose is a component of many biologically important substances, most notably the ribonucleic acids, and D-xylose is very abundant and is isolated by hydrolysis of the polysaccharides present in corncobs and the wood of trees.

The aldohexoses include some of the most familiar of the monosaccharides, as well as one of the most abundant organic compounds on earth, D-( )-glucose. With four stereogenic centers, 16 stereoisomeric aldohexoses are possible; 8 belong to the Dseries and 8 to the Lseries. All are known, either as naturally occurring substances or as the products of synthesis. The eight D-aldohexoses are given in Figure 25.2; it is the spatial arrangement at C-5, hydrogen to the left in a Fischer projection and hydroxyl to the right, that identifies them as carbohydrates of the Dseries.

PROBLEM 25.4Name the following sugar:

Of all the monosaccharides, D-( )-glucoseis the best known, most important, and most abundant. Its formation from carbon dioxide, water, and sunlight is the central theme of photosynthesis. Carbohydrate formation by photosynthesis is estimated to be on the order of 1011tons per year, a source of stored energy utilized, directly or indirectly, by all higher forms of life on the planet. Glucose was isolated from raisins in 1747 and by hydrolysis of starch in 1811. Its structure was determined, in work culminating in 1900, by Emil Fischer.

D-( )-Galactoseis a constituent of numerous polysaccharides. It is best obtained by acid hydrolysis of lactose (milk sugar), a disaccharide of D-glucose and D-galactose.


976 CHAPTER TWENTY-FIVE Carbohydrates

Cellulose is more abundant than glucose, but each cellulose molecule is a polysaccharide composed of thousands of glucose units (Section 25.15). Methane may also be more abundant, but most of the methane comes from glucose.

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25.4 Aldopentoses and Aldohexoses



CH 2


CH 2


CH 2

2 OH



FIGURE 25.2 Con-fi gurations of the D series of aldosescontaining threethrough six carbonatoms.



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L( )-Galactose also occurs naturally and can be prepared by hydrolysis of flaxseed gum and agar. The principal source of D-( )-mannoseis hydrolysis of the polysaccharide of the ivory nut, a large, nut-like seed obtained from a South American palm.


The task of relating carbohydrate configurations to names requires either a world-class memory or an easily recalled mnemonic. Amnemonic that serves us well here was popularized by the husband–wife team of Louis F. Fieser and Mary Fieser of Harvard University in their 1956 textbook, Organic Chemistry.As with many mnemonics, it’s not clear who actually invented it, and references to this particular one appeared in the chemical education literature before publication of the Fiesers’text. The mnemonic has two features: (1) a system for setting down all the stereoisomeric D-aldohexoses in a logical order; and (2) a way to assign the correct name to each one.

Asystematic way to set down all the D-hexoses (as in Fig. 25.2) is to draw skeletons of the necessary eight Fischer projections, placing the hydroxyl group at C-5 to the right in each so as to guarantee that they all belong to the Dseries. Working up the carbon chain, place the hydroxyl group at C-4 to the right in the first four structures, and to the left in the next four. In each of these two sets of four, place the C-3 hydroxyl group to the right in the first two and to the left in the next two; in each of the resulting four sets of two, place the C-2 hydroxyl group to the right in the first one and to the left in the second.

Once the eight Fischer projections have been written, they are named in order with the aid of the sentence: All altruists gladly make gum in gallon tanks. The words of the sentence stand for allose, altrose, glucose, mannose, gulose, idose, galactose, talose.

An analogous pattern of configurations can be seen in the aldopentoses when they are arranged in the order ribose, arabinose, xylose, lyxose.(RAXLis an easily remembered nonsense word that gives the correct sequence.) This pattern is discernible even in the aldotetroses erythrose and threose.


Aldoses incorporate two functional groups, CœO and OH, which are capable of reacting with each other. We saw in Section 17.8 that nucleophilic addition of an alcohol function to a carbonyl group gives a hemiacetal. When the hydroxyl and carbonyl groups are part of the same molecule, a cyclic hemiacetalresults, as illustrated in Figure 25.3.

Cyclic hemiacetal formation is most common when the ring that results is five- or six-membered. Five-membered cyclic hemiacetals of carbohydrates are called furanose forms; six-membered ones are called pyranoseforms. The ring carbon that is derived from the carbonyl group, the one that bears two oxygen substituents, is called the anomeric carbon.

Aldoses exist almost exclusively as their cyclic hemiacetals; very little of the openchain form is present at equilibrium. To understand their structures and chemical reactions, we need to be able to translate Fischer projections of carbohydrates into their cyclic hemiacetal forms. Consider first cyclic hemiacetal formation in D-erythrose. So as to visualize furanose ring formation more clearly, redraw the Fischer projection in a form more suited to cyclization, being careful to maintain the stereochemistry at each stereogenic center.

(Parte 1 de 6)