CHAPTER 25 CARBOHYDRATES he major classes of organic compounds common to living systems are lipids, pro- teins, 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. Carbohy drates 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'll 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 aldehyde or polyhydro ketone, a point of view closer to structural reality and more suggestive of chemical reac- tivity. 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 confor- mational analysis combine to aid our understanding of this complex subject. The remain- der 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 25.1 CLASSIFICATION OF CARBOHYDRATES The Latin word for"sugar"*is saccharum, and the derived term "saccharide"is the basis of a system of carbohydrate classification. A monosaccharide is a simple carbohydrate, one that on attempted hydrolysis is not cleaved to smaller carbohydrates. Glucose r"is a combination of the Sanskrit words su(sweet)and gar (sand). Thus, its literal meaning is"sweet 972 Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
CHAPTER 25 CARBOHYDRATES 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’ll 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 aldehyde or 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. 25.1 CLASSIFICATION OF CARBOHYDRATES The Latin word for “sugar”* is saccharum, and the derived term “saccharide” is the basis of a system of carbohydrate classification. A monosaccharide is a simple carbohydrate, one that on attempted hydrolysis is not cleaved to smaller carbohydrates. Glucose 972 *“Sugar” is a combination of the Sanskrit words su (sweet) and gar (sand). Thus, its literal meaning is “sweet sand.” Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
25.2 Fischer Projections and D-L Notation (C6H12O6), for example, is a monosaccharide. a disaccharide on hydrolysis is cleaved to two monosaccharides, which may be the same or different. Sucrose--common table ugar-is a disaccharide that yields one molecule of glucose and one of fructose on hydrolysis Sucrose(C12H22O11)+ H20- glucose(C6H1206)+ fructose(C6H12O6) An oligosaccharide(oligos is a greek word that in its plural form means"few") yields 3-10 monosaccharide units on hydrolysis. Polysaccharides are hydrolyzed to more than 10 monosaccharide units. Cellulose is 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 alde hydes 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 25.2 FISCHER PROJECTIONS AND D-L NOTATION 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 determined the struc Fischer to represent stereochemistry in chiral molecules are particularly well-suited to ture of gl studying carbohydrates. Figure 25 1 illustrates their application to the enantiomers of won the Nobse in 1900 and glyceraldehyde(2, 3-dihydroxypropanal), a fundamental molecule in carbohydrate stereo- chemistry. When the Fischer projection is oriented as shown in the figure, with the car bon 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. A system evolved based on the arbitrary assumption, later shown to be correct, that the enantiomers ure 25.1. Two stereochemical descriptors were defined: D and L. The absolute configu- glyceraldehyde as stereo rs of of glyceraldehyde have the signs of rotation and absolute configurations shown in Fig-Ade ration of(+)glyceraldehyde, as depicted in the figure, was said to be d and that of its pounds originated with enantiomer,(-)glyceraldehyde, L Compounds that had a spatial arrangement of sub- proposals made in 1906 by stituents analogous to D-(+)-and L-(-)-glyceraldehyde were said to have the D and L configurations, respectively. New York University. TABLE 25.1 Some Classes of Monosaccharides Number of carbon atoms Aldose Ketose Aldotetrose Ketotetrose Aldopentose Ketopentose Aldohexose Ketohexose Seven Aldoheptose Ketoheptose Eight Aldooctose Ketooctos Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
(C6H12O6), for example, is a monosaccharide. A disaccharide on 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 (oligos is a Greek word that in its plural form means “few”) yields 3–10 monosaccharide units on hydrolysis. Polysaccharides are hydrolyzed to more than 10 monosaccharide units. Cellulose is 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. 25.2 FISCHER PROJECTIONS AND D–L NOTATION 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. A system 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: D and L. The absolute configuration of ()-glyceraldehyde, as depicted in the figure, was said to be D and 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 D and L configurations, respectively. Sucrose (C12H22O11) H 2O glucose (C6H12O6) fructose ( C6H12O6) 25.2 Fischer Projections and D–L Notation 973 TABLE 25.1 Some Classes of Monosaccharides Aldose Aldotetrose Aldopentose Aldohexose Aldoheptose Aldooctose Ketose 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. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
CHAPTER TWENTY-FIVE Carbohydrat CH=O CH=O FIGURE 25.1 Three- dimensional representations H OH OH and Fischer projections of the enantiomers of glycer CH,OH R-(+)-Glyceraldehyde CH=O CH=O HO- H HO CH,O PROBLEM 25.1 Identify each of the following as either D-or L-glyceraldehyde (b) CHO CHO 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. CH2OH CHO CH2OH is equivalent to HOrC-H -OH CHO CHO CH2OH The structure is the same as that of (+)-glyceraldehyde in the figure. It is D- glyceraldehyde. ischer projections and D-L notation 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 25.3 THE ALDOTETROSES Glyceraldehyde can be considered to be the simplest chiral carbohydrate. It is an aldotriose and, since it contains one stereogenic center, exists in two stereoisomeri orms: the D and L enantiomers. Moving up the scale in complexity, next come the aldotetroses. Examination of their structures illustrates the application of the Fischer sys- tem to compounds that contain more than one stereogenic center. The aldotetroses are the four stereoisomers of 2, 3, 4-trihydroxybutanal. Fischer pro- Molecular models of th jections are constructed by orienting the molecule in an eclipsed conformation with the may be viewed on the CD the aldehyde group at what will be the top. The four carbon atoms define the main chain of accompanies this tex the Fischer projection and are arranged vertically. Horizontal bonds are directed outward, vertical bonds back Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
PROBLEM 25.1 Identify 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 Dglyceraldehyde. Fischer projections and D–L notation 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. 25.3 THE ALDOTETROSES Glyceraldehyde can be considered to be the simplest chiral carbohydrate. It is an aldotriose and, since it contains one stereogenic center, exists in two stereoisomeric forms: the D and L enantiomers. 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. HO H CH2OH CHO is equivalent to turn 180° HO C CH2OH H CHO H C CHO OH CH2OH HOCH2 OH H CHO HOCH2 CHO H OH HO H CH2OH CHO 974 CHAPTER TWENTY-FIVE Carbohydrates CHœO CH2OH OH CHœO CHœO HO HO H H H CH2OH R-(+)-Glyceraldehyde S-(–)-Glyceraldehyde H C OH CHœO CH2OH C CH2OH 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. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
25.3 The aldotetroses CHOOH CHO CHO is equivalent to H CHOH CHOH CH,OHOH Fischer projection of a tetrose Eclipsed conformation The particular aldotetrose just shown is called D-erythrose. The prefix D tells us that the configuration at the highest numbered stereogenic center is analogous to that of D-(+)- the development of syste glyceraldehyde. Its mirror image is L-erythrose atic carbohydrate nomencla- ture see C.D. Hurd 's article in the december 1989 issue CHO ducation, pp. 984-988. tereogenic center HOH has configuration OH HO -H analogous to that of D-glyceraldehyde L-glyceraldehyde CH,OH CH2OH Relative to each other, both hydroxyl groups are on the same side in Fischer pro- jections 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 D and l prefixes again specify the con- figuration of the highest numbered stereogenic center. D-Threose and L-threose are enan- tiomers of each other. CHO CHO nter HO OH stereogenic center OH HO H D-glyceraldehyde L-glyceraldehyde CHOH CHOH D-Threose L-Threose PROBLEM 25.2 Which 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. Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
The particular aldotetrose just shown is called D-erythrose. The prefix D tells us that the configuration at the highest numbered stereogenic center is 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 D and L prefixes again specify the con- figuration of the highest numbered stereogenic center. D-Threose and L-threose are enantiomers of each other: PROBLEM 25.2 Which 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.) 1 2 3 4 Highest numbered stereogenic center has configuration analogous to that of D-glyceraldehyde HO H CHO CH2OH H OH 4 3 2 1 D-Threose H OH CHO CH2OH HO H 4 3 2 1 L-Threose Highest numbered stereogenic center has configuration analogous to that of L-glyceraldehyde Highest numbered stereogenic center has configuration analogous to that of D-glyceraldehyde H CHO CH2OH OH H OH 4 3 2 1 D-Erythrose H CHO CH2OH HO HO H 4 3 2 1 L-Erythrose Highest numbered stereogenic center has configuration analogous to that of L-glyceraldehyde which is written as H C C CHO CH2OH H OH OH H CHO CH2OH OH H OH Fischer projection of a tetrose is equivalent to 25.3 The Aldotetroses 975 Eclipsed conformation of a tetrose CH2OH CHO OH OH H H 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, pp. 984–988. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
CHAPTER TWENTY-FIVE Carbohydrat As shown for the aldotetroses, an aldose belongs to the d or the L series accord- ing to the configuration of the stereogenic center farthest removed from the aldehyde function. Individual names, such as erythrose and threose, specify the particular arrange- ment of stereogenic centers within the molecule relative to each other. Optical activities cannot be determined directly from the D and L prefixes. As it turns out, both D-erythrose and D-threose are levorotatory, but D-glyceraldehyde is dextrorotatory 25.4 ALDOPENTOSES AND ALDOHEXOSES Aldopentoses have three stereogenic centers. The eight stereoisomers are divided into a et of four D-aldopentoses and an enantiomeric set of four L-aldopentoses. The aldopen- toses 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 diastereo- mers have the same configuration at C-4 and that this configuration is analogous to that of D-(+)-glyceraldehyde PROBLEM 25.3 L-(+)-Arabinose is a naturally occurring L sugar. It is obtained by acid hydrolysis of the polysaccharide present in mesquite gum. Write a Fischer pro- jection 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 iso- lated 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 than glucose, but each cellu- as one of the most abundant organic compounds on earth, D-(+)-glucose. With four lose molecule is a polysac- charide composed of stereogenic centers, 16 stereoisomeric aldohexoses are possible: 8 belong to the D series housands of glucose units and 8 to the L series. All are known, either as naturally occurring substances or as the Section 25. 15). metha products of synthesis. The eight D-aldohexoses are given in Figure 25.2; it is the spatia ay also be more abundant, arrangement at C-5, hydrogen to the left in a Fischer projection and hydroxyl to the right, comes from glucose. that identifies them as carbohydrates of the D series PROBLEM 25.4 Name the following sugar CHO CHOH Of all the monosaccharides, D-(+)-glucose is 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 10 tons per year, a source of stored energy utilized, directly or indi rectly, 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 culmi- nating in 1900, by Emil Fischer. D-(+)-Galactose is a constituent of numerous polysaccharides. It is best obtained by acid hydrolysis of lactose(milk sugar), a disaccharide of D-glucose and D-galactose Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
As shown for the aldotetroses, an aldose belongs to the D or the L series 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 D and L prefixes. As it turns out, both D-erythrose and D-threose are levorotatory, but D-glyceraldehyde is dextrorotatory. 25.4 ALDOPENTOSES AND ALDOHEXOSES 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 25.3 L-()-Arabinose is a naturally occurring L sugar. 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 D series and 8 to the L series. 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 D series. PROBLEM 25.4 Name the following sugar: Of all the monosaccharides, D-()-glucose is 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 1011 tons 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-()-Galactose is a constituent of numerous polysaccharides. It is best obtained by acid hydrolysis of lactose (milk sugar), a disaccharide of D-glucose and D-galactose. H OH CHO H OH H OH HO H CH2OH 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. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website