885c07-238-27211/21/037:38 AM Page238Mac113mac11:4EDL chapter CARBOHYDRATES AND GLYCOBIOLOGY 7.1 Monosaccharides and disaccharides 239 attached to proteins or lipids act as signals that deter 7.2 Polysaccharides 247 mine the intracellular location or metabolic fate of these hybrid molecules, called glycoconjugates. This chap 7.3 Glycoconjugates: Proteoglycans, Glycoproteins, ter introduces the major classes of carbohydrates and glycoconjugates and provides a few examples of their 7.4 Carbohydrates as Informational Molecules: many structural and functional roles The Sugar Code 261 Carbohydrates are polyhydroxy aldehydes or ke- 7.5 Working with Carbohydrates 267 tones, or substances that yield such compounds on hy drolysis. Many, but not all, carbohydrates have the em- pirical formula (CHOni some also contain nitrogen, Ah! sweet mystery of life phosphorus, or sulfur. -Rida Johnson Young(lyrics)and Victor Herbert(music), There are three major size classes of carbohydrates Ah! Sweet Mystery of Life, 1910 monosaccharides, oligosaccharides, and polysaccha rides(the word"saccharide"is derived from the greek sakcharom, meaning"sugar). Monosaccharides, or I would feel more optimistic about a bright future for man simple sugars, consist of a single polyhydroxy aldehyde if he spent less time proving that he can outwit Nature or ketone unit. The most abundant monosaccharide in and more time tasting her sweetness and respecting her nature is the six-carbon sugar D-glucose, sometimes re- ferred to as dextrose. Monosaccharides of more than -E.B. White. "Coon Tree. "1977 four carbons tend to have cyclic structures Oligosaccharides consist of short chains of mono- saccharide units, or residues, joined by characteristic carbohydrates are the most abundant biomolecules linkages called glycosidic bonds. The most abundant are on Earth. Each year, photosynthesis converts more the disaccharides, with two monosaccharide units than 100 billion metric tons of COe and HO into cellu- Typical is sucrose(cane sugar), which consists of the lose and other plant products. Certain carbohydrates six-carbon sugars D-glucose and D-fructose. All common (sugar and starch) are a dietary staple in most parts of monosaccharides and disaccharides have names ending the world, and the oxidation of carbohydrates is the cen- with the suffix "-ose "In cells, most oligosaccharides tral energy-yielding pathway in most nonphotosynthetic consisting of three or more units do not occur as free cells. Insoluble carbohydrate polymers serve as struc- entities but are joined to nonsugar molecules (lipids or tural and protective elements in the cell walls of bacte- proteins) in glycoconjugates ria and plants and in the connective tissues of animals. The polysaccharides are sugar polymers contain- Other carbohydrate polymers lubricate skeletal joints ing more than 20 or so monosaccharide units, and some and participate in recognition and adhesion between have hundreds or thousands of units. Some polysac cells. More complex carbohydrate polymers covalently charides, such as cellulose, are linear chains; others
chapter Carbohydrates are the most abundant biomolecules on Earth. Each year, photosynthesis converts more than 100 billion metric tons of CO2 and H2O into cellulose and other plant products. Certain carbohydrates (sugar and starch) are a dietary staple in most parts of the world, and the oxidation of carbohydrates is the central energy-yielding pathway in most nonphotosynthetic cells. Insoluble carbohydrate polymers serve as structural and protective elements in the cell walls of bacteria and plants and in the connective tissues of animals. Other carbohydrate polymers lubricate skeletal joints and participate in recognition and adhesion between cells. More complex carbohydrate polymers covalently attached to proteins or lipids act as signals that determine the intracellular location or metabolic fate of these hybrid molecules, called glycoconjugates. This chapter introduces the major classes of carbohydrates and glycoconjugates and provides a few examples of their many structural and functional roles. Carbohydrates are polyhydroxy aldehydes or ketones, or substances that yield such compounds on hydrolysis. Many, but not all, carbohydrates have the empirical formula (CH2O)n; some also contain nitrogen, phosphorus, or sulfur. There are three major size classes of carbohydrates: monosaccharides, oligosaccharides, and polysaccharides (the word “saccharide” is derived from the Greek sakcharon, meaning “sugar”). Monosaccharides, or simple sugars, consist of a single polyhydroxy aldehyde or ketone unit. The most abundant monosaccharide in nature is the six-carbon sugar D-glucose, sometimes referred to as dextrose. Monosaccharides of more than four carbons tend to have cyclic structures. Oligosaccharides consist of short chains of monosaccharide units, or residues, joined by characteristic linkages called glycosidic bonds. The most abundant are the disaccharides, with two monosaccharide units. Typical is sucrose (cane sugar), which consists of the six-carbon sugars D-glucose and D-fructose. All common monosaccharides and disaccharides have names ending with the suffix “-ose.” In cells, most oligosaccharides consisting of three or more units do not occur as free entities but are joined to nonsugar molecules (lipids or proteins) in glycoconjugates. The polysaccharides are sugar polymers containing more than 20 or so monosaccharide units, and some have hundreds or thousands of units. Some polysaccharides, such as cellulose, are linear chains; others, CARBOHYDRATES AND GLYCOBIOLOGY 7.1 Monosaccharides and Disaccharides 239 7.2 Polysaccharides 247 7.3 Glycoconjugates: Proteoglycans, Glycoproteins, and Glycolipids 255 7.4 Carbohydrates as Informational Molecules: The Sugar Code 261 7.5 Working with Carbohydrates 267 Ah! sweet mystery of life . . . —Rida Johnson Young (lyrics) and Victor Herbert (music), “Ah! Sweet Mystery of Life,” 1910 I would feel more optimistic about a bright future for man if he spent less time proving that he can outwit Nature and more time tasting her sweetness and respecting her seniority. —E. B. White, “Coon Tree,” 1977 7 238 8885d_c07_238-272 11/21/03 7:38 AM Page 238 Mac113 mac113:122_EDL:
885d_c07-238-27211/21/037:38 AM Page239Mac113mac113:1aEDL Chapter 7 Carbohydrates and Glycobiology such as glycogen, are branched. Both glycogen and cel lulose consist of recurring units of D-glucose, but they differ in the type of glycosidic linkage and consequently have strikingly different properties and biological roles -C-OH H-C-OH H-C-OH 7. 1 Monosaccharides and disaccharides Glyceraldehyde, Dihydroxyacetone The simplest of the carbohydrates, the monosaccha rides, are either aldehydes or ketones with two or more ydroxyl groups; the six-carbon monosaccharides glu cose and fructose have five hydroxyl groups. Many of the carbon atoms to which hydroxyl groups are attached -C-OH are chiral centers, which give rise to the many sugar H-C-OH stereoisomers found in nature. We begin by describing HO-C-H HO-C-H the families of monosaccharides with backbones of three to seven carbons-their structure and stereoisomeric H-C-OH H-C-OH forms, and the means of representing their three- H-C-OH H-C-OH imensional structures on paper. We then discuss sev CH,OH CHOH eral chemical reactions of the carbonyl groups of mono- saccharides. One such reaction the addition of a hydroxyl group from within the same molecule, gener- ates the cyclic forms of five- and six-carbon sugars(the forms that predominate in aqueous solution) and cre- H ates a new chiral center, adding further stereochemical complexity to this class of compounds. The nomencla- HC-OH ture for unambiguously specifying the configuration about each carbon atom in a cyclic form and the means H-C-OH H-C-OH of representing these structures on paper are therefore H-C-OH H-C- described in some detail: this information willl be useful as we discuss the metabolism of monosaccharides in CHOOH CHOH Part Il. We also introduce here some important mono- an aldopentose saccharide derivatives encountered in later chapters. The Two Families of monosaccharides are aldoses FIGURE 7-1 Representative monosaccharides. (a) Two trioses, an and Ketoses aldose and a ketose. The carbonyl group in each is shaded. (b)Two common hexoses. (c) The pentose components of nucleic acids Monosaccharides are colorless, crystalline solids that D-Ribose is a component of ribonucleic acid(RNA), and 2-deoxy-D- are freely soluble in water but insoluble in nonpolar sol ribose is a component of deoxyribonucleic acid (DNA) vents. Most have a sweet taste. The backbones of com- mon monosaccharide molecules are unbranched carbon chains in which all the carbon atoms are linked by sin- aldotetroses and ketotetroses, aldopentoses and ke- gle bonds. In the open-chain form, one of the carbon topentoses, and so on. The hexoses, which include the atoms is double-bonded to an oxygen atom to form a aldohexose D-glucose and the ketohexose D-fructose carbonyl group; each of the other carbon atoms has a (Fig. 7-1b), are the most common monosaccharides in hydroxyl group. If the carbonyl group is at an end of the ture. The aldopentoses D-ribose and 2-deoxy-D-ribose carbon chain(that is, in an aldehyde group) the mono- (Fig. 7-lc)are components of nucleotides and nucleic saccharide is an aldose; if the carbonyl group is at any acids(Chapter 8) other position (in a ketone group) the monosaccharide is a ketose. The simplest monosaccharides are the two Monosaccharides Have Asymmetric Centers three-carbon trioses: glyceraldehyde, an aldotriose, and All the monosaccharides except dihydroxyacetone con dihydroxyacetone, a ketotriose(Fig. 7-la) tain one or more asymmetric(chiral) carbon atoms and Monosaccharides with four, five, six, and seven car- thus occur in optically active isomeric forms(pp. 17- bon atoms in their backbones are called, respectively, 19). The simplest aldose, glyceraldehyde, contains one tetroses, pentoses, hexoses, and heptoses. There are chiral center (the middle carbon atom) and therefore has aldoses and ketoses of each of these chain lengths: two different optical isomers, or enantiomers(Fig. 7-2)
Chapter 7 Carbohydrates and Glycobiology 239 such as glycogen, are branched. Both glycogen and cellulose consist of recurring units of D-glucose, but they differ in the type of glycosidic linkage and consequently have strikingly different properties and biological roles. 7.1 Monosaccharides and Disaccharides The simplest of the carbohydrates, the monosaccharides, are either aldehydes or ketones with two or more hydroxyl groups; the six-carbon monosaccharides glucose and fructose have five hydroxyl groups. Many of the carbon atoms to which hydroxyl groups are attached are chiral centers, which give rise to the many sugar stereoisomers found in nature. We begin by describing the families of monosaccharides with backbones of three to seven carbons—their structure and stereoisomeric forms, and the means of representing their threedimensional structures on paper. We then discuss several chemical reactions of the carbonyl groups of monosaccharides. One such reaction, the addition of a hydroxyl group from within the same molecule, generates the cyclic forms of five- and six-carbon sugars (the forms that predominate in aqueous solution) and creates a new chiral center, adding further stereochemical complexity to this class of compounds. The nomenclature for unambiguously specifying the configuration about each carbon atom in a cyclic form and the means of representing these structures on paper are therefore described in some detail; this information will be useful as we discuss the metabolism of monosaccharides in Part II. We also introduce here some important monosaccharide derivatives encountered in later chapters. The Two Families of Monosaccharides Are Aldoses and Ketoses Monosaccharides are colorless, crystalline solids that are freely soluble in water but insoluble in nonpolar solvents. Most have a sweet taste. The backbones of common monosaccharide molecules are unbranched carbon chains in which all the carbon atoms are linked by single bonds. In the open-chain form, one of the carbon atoms is double-bonded to an oxygen atom to form a carbonyl group; each of the other carbon atoms has a hydroxyl group. If the carbonyl group is at an end of the carbon chain (that is, in an aldehyde group) the monosaccharide is an aldose; if the carbonyl group is at any other position (in a ketone group) the monosaccharide is a ketose. The simplest monosaccharides are the two three-carbon trioses: glyceraldehyde, an aldotriose, and dihydroxyacetone, a ketotriose (Fig. 7–1a). Monosaccharides with four, five, six, and seven carbon atoms in their backbones are called, respectively, tetroses, pentoses, hexoses, and heptoses. There are aldoses and ketoses of each of these chain lengths: aldotetroses and ketotetroses, aldopentoses and ketopentoses, and so on. The hexoses, which include the aldohexose D-glucose and the ketohexose D-fructose (Fig. 7–1b), are the most common monosaccharides in nature. The aldopentoses D-ribose and 2-deoxy-D-ribose (Fig. 7–1c) are components of nucleotides and nucleic acids (Chapter 8). Monosaccharides Have Asymmetric Centers All the monosaccharides except dihydroxyacetone contain one or more asymmetric (chiral) carbon atoms and thus occur in optically active isomeric forms (pp. 17– 19). The simplest aldose, glyceraldehyde, contains one chiral center (the middle carbon atom) and therefore has two different optical isomers, or enantiomers (Fig. 7–2). H C O OH Dihydroxyacetone, a ketotriose A C OH C H H H H C OH A H C OH H Glyceraldehyde, an aldotriose O C H (a) (b) D-Fructose, a ketohexose C O OH C C H C H H HO CH2OH H OH H C OH D-Glucose, an aldohexose C OH C C H H HO CH2OH H OH H C OH O C H (c) 2-Deoxy-D-ribose, an aldopentose C OH O C H H CH2 H C OH D-Ribose, an aldopentose C OH H C H CH2OH OH H C OH CH2OH O C H FIGURE 7–1 Representative monosaccharides. (a) Two trioses, an aldose and a ketose. The carbonyl group in each is shaded. (b) Two common hexoses. (c) The pentose components of nucleic acids. D-Ribose is a component of ribonucleic acid (RNA), and 2-deoxy-Dribose is a component of deoxyribonucleic acid (DNA). 8885d_c07_238-272 11/21/03 7:38 AM Page 239 Mac113 mac113:122_EDL:
885d_c07-238-27211/21/037:38 AM Page240Mac113mac113:1aEDL 240 Part I Structure and Catalysis of each carbon-chain length can be divided into two groups that differ in the configuration about the chiral center most distant from the carbonyl carbon. Those in which the configuration at this reference carbon is the same as that of D-glyceraldehyde are designated D CHO CHO isomers, and those with the same configuration as L- glyceraldehyde are L isomers. When the hydroxyl group on the reference carbon is on the right in the projection formula, the sugar is the D isomer; when on the left, it is the L isomer Of the 16 possible aldohexoses, eight are D forms and eight are L. Most of the hexoses of living organisms are D isomers CH2OH Figure 7-3 shows the structures of the D stereoiso- mers of all the aldoses and ketoses having three to six carbon atoms. The carbons of a sugar are numbered be- ginning at the end of the chain nearest the carbonyl Ball-and-stick models group. Each of the eight D-aldohexoses, which differ in the stereochemistry at C-2, C-3, or C-4, has its own name: D-glucose, D-galactose, D-mannose, and so forth CHO CHO (Fig. 7-3a). The four- and five-carbon ketoses are des H-C-OH HO--C-H ignated by inserting"ul"into the name of a correspond ing aldose; for example, D-ribulose is the ketopentose CH,OH CH,OH corresponding to the aldopentose D-ribose. The keto- hexoses are named otherwise: for example, fructose (from the Latin fructus, fruit"; fruits are rich in this Fischer projection formulas sugar) and sorbose (from Sorbus, the genus of moun- tain ash, which has berries rich in the related sugar al- cohol sorbitol). Two sugars that differ only in the con figuration around one carbon atom are called epimers; H-C-OH HO-C-H D-glucose and D-mannose, which differ only in the stere- ochemistry at C-2, are epimers, as are D-glucose and D- CHOH CH。OH galactose(which differ at C-4)(Fig. 7-4) L-Glyceraldehyde Some sugars occur naturally in their L form; exam ples are L-arabinose and the L isomers of some sugar de- rivatives that are common components of glycoconju- FIGURE 7-2 Three ways to represent the two stereoisomers of glyc- gates(Section 7.3) eraldehyde. The stereoisomers are mirror images of each other. Ball- H O and-stick models show the actual configuration of molecules By con- vention, in Fischer projection formulas, horizontal bonds project out H-C-OHl of the plane of the paper, toward the reader; vertical bonds project ehind the plane of the paper, away from the reader. Recall (see Fig HO-C-H 1-17)that in perspective formulas, solid wedge-shaped bonds point toward the reader, dashed wedges point away CHOH By convention, one of these two forms is designated the The Common Monosaccharides D isomer the other the l isomer. as for other biomole cules with chiral centers, the absolute configurations of Have Cyclic Structures sugars are known from x-ray crystallography. To repre- For simplicity, we have thus far represented the struc sent three-dimensional sugar structures on paper, we tures of aldoses and ketoses as straight-chain molecules often use Fischer projection formulas (Fig. 7-2) (Figs 7-3, 7-4). In fact, in aqueous solution, aldotet- In general, a molecule with n chiral centers can roses and all monosaccharides with five or more carbon have 2" stereoisomers. Glyceraldehyde has 2=2; the atoms in the backbone occur predominantly as cyclic aldohexoses, with four chiral centers, have 2=16 (ring) structures in which the carbonyl group has stereoisomers. The stereoisomers of monosaccharides formed a covalent bond with the oxygen of a hydroxyl
By convention, one of these two forms is designated the D isomer, the other the L isomer. As for other biomolecules with chiral centers, the absolute configurations of sugars are known from x-ray crystallography. To represent three-dimensional sugar structures on paper, we often use Fischer projection formulas (Fig. 7–2). In general, a molecule with n chiral centers can have 2n stereoisomers. Glyceraldehyde has 21 2; the aldohexoses, with four chiral centers, have 24 16 stereoisomers. The stereoisomers of monosaccharides of each carbon-chain length can be divided into two groups that differ in the configuration about the chiral center most distant from the carbonyl carbon. Those in which the configuration at this reference carbon is the same as that of D-glyceraldehyde are designated D isomers, and those with the same configuration as Lglyceraldehyde are L isomers. When the hydroxyl group on the reference carbon is on the right in the projection formula, the sugar is the D isomer; when on the left, it is the L isomer. Of the 16 possible aldohexoses, eight are D forms and eight are L. Most of the hexoses of living organisms are D isomers. Figure 7–3 shows the structures of the D stereoisomers of all the aldoses and ketoses having three to six carbon atoms. The carbons of a sugar are numbered beginning at the end of the chain nearest the carbonyl group. Each of the eight D-aldohexoses, which differ in the stereochemistry at C-2, C-3, or C-4, has its own name: D-glucose, D-galactose, D-mannose, and so forth (Fig. 7–3a). The four- and five-carbon ketoses are designated by inserting “ul” into the name of a corresponding aldose; for example, D-ribulose is the ketopentose corresponding to the aldopentose D-ribose. The ketohexoses are named otherwise: for example, fructose (from the Latin fructus, “fruit”; fruits are rich in this sugar) and sorbose (from Sorbus, the genus of mountain ash, which has berries rich in the related sugar alcohol sorbitol). Two sugars that differ only in the configuration around one carbon atom are called epimers; D-glucose and D-mannose, which differ only in the stereochemistry at C-2, are epimers, as are D-glucose and Dgalactose (which differ at C-4) (Fig. 7–4). Some sugars occur naturally in their L form; examples are L-arabinose and the L isomers of some sugar derivatives that are common components of glycoconjugates (Section 7.3). The Common Monosaccharides Have Cyclic Structures For simplicity, we have thus far represented the structures of aldoses and ketoses as straight-chain molecules (Figs 7–3, 7–4). In fact, in aqueous solution, aldotetroses and all monosaccharides with five or more carbon atoms in the backbone occur predominantly as cyclic (ring) structures in which the carbonyl group has formed a covalent bond with the oxygen of a hydroxyl L-Arabinose C O A A A A O O O C OH H OCO H HO H CH2OH HO O C H G J 240 Part I Structure and Catalysis FIGURE 7–2 Three ways to represent the two stereoisomers of glyceraldehyde. The stereoisomers are mirror images of each other. Balland-stick models show the actual configuration of molecules. By convention, in Fischer projection formulas, horizontal bonds project out of the plane of the paper, toward the reader; vertical bonds project behind the plane of the paper, away from the reader. Recall (see Fig. 1–17) that in perspective formulas, solid wedge-shaped bonds point toward the reader, dashed wedges point away. Mirror CH2OH Ball-and-stick models CH2OH CHO CHO OH H H OH CHO C H CH2OH HO L-Glyceraldehyde Perspective formulas L-Glyceraldehyde C CH2OH H CHO CHO CHO H C OH CH2OH D-Glyceraldehyde OH D-Glyceraldehyde C CH2OH H HO Fischer projection formulas 8885d_c07_238-272 11/21/03 7:38 AM Page 240 Mac113 mac113:122_EDL:
885d_c07-238-27211/21/037:38 AM Page241Mac113mac113:1aEDL Chapter 7 Carbohydrates and Glycobiology 241 Four carbons Five carbons H O H 0 H O H O H-C-oH HO- H-C-oH HO-C-H H-C-oH H--C-OH HO H-C-OH H-C-OH H→C-OH H-C-OH H OH HoH OH D-Glyceraldehyde D-ErythroseD-Threose D-Ribose [D-Arabinose Xylo L Six carbons H O H O H 0 H O H O H H O H O H-C-OH o-C-H OHHo→-H HC- OH HO-C—H H-C-OH HO-C-H H--C-O H-C-oH HO-C-H HO→C-H H-C-oHH-C-oh HO-C-H HO-C-H H-C-ohH-C-oh H-C-oh H-C-oh HO--C-H Ho--C-h Ho--c-h Ho-C-H OH H-C-oH H-C-oH H-C-oH H-C-oH H-C-oH D-Glucose D-Mannose D-Gulose D-Idose D-Galactose DAldoses Three carbons our carbons FIGURE 7-3 Aldoses and ketoses. The series of (a)D-aldoses and (b)Ketoses having from three to six carbon atoms, shown as CH2OH projection formulas. The carbon atoms in red are chiral centers. In all these D isomers, the chiral carbon most distant from the carbonyl carbon has the same configuration as the chiral carbon OH in D-glyceraldehyde. The sugars named in boxes are the most Dihydroxyacetone common in nature; you will encounter these again in this and Five carbons Six carbons CHOH CHoO CHOO C=0 H-C-OH O-C-H H-C-OH H-C-OH H-C-OH -C-OH D-Ribulose cho CHO H-C-OH H-C-OHI CHoO CHoO HO-°C-H CH,OH C-O H-C-OH HOC—H C=O HO-C-H H-C-OH HOH D-Glucose D-Galactose CH2OH CH2OH at C-2) (epimer at C-4) D-Xylulose D-Sorbose FIGURE 7-4 Epimers. D-Glucose and two of its epimers are shown D-Ketoses as projection formulas. Each epimer differs from D-glucose in the con figuration at one chiral center(shaded red)
Chapter 7 Carbohydrates and Glycobiology 241 D-Aldoses (a) Six carbons Three carbons H O C H C OH CH2OH D-Ribose H C OH H OH C H C O OH CH2OH D-Glyceraldehyde H C C H O CH2OH D-Threose C H C OH HO H H C O OH CH2OH D-Erythrose H C H C OH H C O OH CH2OH D-Allose C H C OH H OH C H C OH H HO C H CH2OH D-Lyxose H C OH C H HO H O C H C OH CH2OH D-Xylose H C OH HO C H H O C C H CH2OH D-Arabinose H C OH H OH C HO H O C C H CH2OH D-Talose H C OH C H C H HO HO HO H O C H C OH CH2OH D-Gulose H C OH C H H C OH HO H O C HO C H CH2OH D-Mannose H C H C OH C H OH HO H O C H C OH CH2OH D-Glucose H C OH H OH C HO C H H O C Four carbons C H CH2OH D-Idose H C OH C H H C OH HO HO H O C H C OH CH2OH D-Galactose H C OH C H HO C H HO H O C C H CH2OH D-Altrose H C OH H OH C H C OH HO O C H Five carbons D-Ketoses (b) H OH O D-Ribulose CH2OH C CH2OH C H C OH H OH O D-Psicose CH2OH C CH2OH C H C OH H C OH HO H O D-Fructose CH2OH C CH2OH C H C OH H C OH H O D-Tagatose CH2OH C CH2OH C H C OH C H HO HO O D-Sorbose CH2OH C CH2OH C OH H C C H HO OH H Dihydroxyacetone CH2OH C CH2OH O Three carbons Five carbons Six carbons Four carbons O D-Xylulose CH2OH C CH2OH C OH H H C HO H OH O D-Erythrulose CH2OH C CH2OH C FIGURE 7–3 Aldoses and ketoses. The series of (a) D-aldoses and (b) D-ketoses having from three to six carbon atoms, shown as projection formulas. The carbon atoms in red are chiral centers. In all these D isomers, the chiral carbon most distant from the carbonyl carbon has the same configuration as the chiral carbon in D-glyceraldehyde. The sugars named in boxes are the most common in nature; you will encounter these again in this and later chapters. H C OH CH2OH D-Mannose (epimer at C-2) C HO C H C CHO 6 1 2 3 4 5 H C OH CH2OH D-Glucose H C HO C H OH H C OH CHO 6 1 2 3 4 5 H C OH CH2OH D-Galactose (epimer at C-4) H C HO C H OH C CHO 6 1 2 3 4 5 H OH HO H HO H FIGURE 7–4 Epimers. D-Glucose and two of its epimers are shown as projection formulas. Each epimer differs from D-glucose in the configuration at one chiral center (shaded red). 8885d_c07_238-272 11/21/03 7:38 AM Page 241 Mac113 mac113:122_EDL:
88607238-2721/21/037:38 AM Page242ac113ac11:aEDL 242 Part I Structure and Catalysis OH HO- o-R =R- R- -C-oR+H,o H Ho—R Aldehyde Alcohol Hemiacetal Acetal FIGURE 7-5 Formation of hemiacetals and hemiketals An aldehyde or ketone can react with an alcohol in a 1:1 ratio to yield a hemiacetal or hemiketal, respectively, creating a new chiral center at the carbonyl carbon. r- -C=0+HO- eRCOR+Ho Substitution of a second alcohol molecule produces HO-R nother sugar molecule, the bond produced is a glycosidic bond (p 245 group along the chain. The formation of these ring struc- istry of ring forms of monosaccharides. However, the tures is the result of a general reaction between alco- six-membered pyranose ring is not planar, as Haworth hols and aldehydes or ketones to form derivatives called perspectives suggest, but tends to assume either of two hemiacetals or hemiketals (Fig. 7-5), which contain"chair" conformations(Fig. 7-8). Recall from Chapter 1 an additional asymmetric carbon atom and thus can ex (p. 19) that two conformations of a molecule are in- ist in two stereoisomeric forms. For example, D-glucose terconvertible without the breakage of covalent bonds exists in solution as an intramolecular hemiacetal in which the free hydroxyl group at C-5 has reacted with the aldehydic C-l, rendering the latter carbon asyn metric and producing two stereoisomers, designated a and B(Fig. 7-6). These six-membered ring compounds are called pyranoses because they resemble the six- membered ring compound pyran(Fig. 7-0. The sys- tematic names for the two ring forms of D-glucose ar a-D-glucopyranose and B-D-glucopyranose H-C-OH Aldohexoses also exist in cyclic forms having five- membered rings, which, because they resemble the five- CH2OH membered ring compound furan, are called furanoses However, the six-membered aldopyranose ring is much more stable than the aldofuranose ring and predomi- CH2OH ates in aldohexose solutions. Only aldoses having five -OH or more carbon atoms can form pyranose rings Isomeric forms of monosaccharides that differ only in their configuration about the hemiacetal or heike- tal carbon atom are called anomers. The hemiacetal (or carbonyl) carbon atom is called the anomeric carbon. The a and B anomers of D-glucose interconvert in aque ous solution by a process called mutarotation. Thus a solution of a-D-glucose and a solution of B-D-glucose eventually form identical equilibrium mixtures having 6CH2OH 6CH2OH identical optical properties. This mixture consists of about one-third a-D-glucose, two-thirds B-D-glucose and very small amounts of the linear and five-membered ring(glucofuranose) forms OH H Ketohexoses also occur in a and B anomeric forms In these compounds the hydroxyl group at C-5(or C-6) reacts with the keto group at C-2, forming a furanose Cor pyranose)ring containing a hemiketal linkage (Fig. FIGURE 7-6 Formation of the two cyclic forms of D-glucose. Read 7-5). D-Fructose readily forms the furanose ring (Fig. tion between the aldehyde group at C-1 and the hydroxyl group at 7-7); the more common anomer of this sugar in com- C-5 forms a hemiacetal linkage, producing either of two stereoiso- bined forms or in derivatives is B-D-fructofuranose mers, the a and B anomers, which differ only in the stereochemistry Haworth perspective formulas like those in Fig- around the hemiacetal carbon. The interconversion of a and B anomers ure 7-7 are commonly used to show the stereochem- is called mutarotation
242 Part I Structure and Catalysis H C -D-Glucopyranose C H OH H 1 5 C 6CH2OH 4 C OH CH2OH 6 C 5 HO H OH C H 3 H C 4 HO C3 OH H H 2 OH C 1 5 6CH2OH 4 C O OH HO OH C H H C3 H C H H 2 OH OH C 1 5 6CH2OH 4 C O HO OH C H H C3 H C H H 2 OH OH D-Glucose -D-Glucopyranose H C O O 1C H 2 FIGURE 7–6 Formation of the two cyclic forms of D-glucose. Reaction between the aldehyde group at C-1 and the hydroxyl group at C-5 forms a hemiacetal linkage, producing either of two stereoisomers, the and anomers, which differ only in the stereochemistry around the hemiacetal carbon. The interconversion of and anomers is called mutarotation. FIGURE 7–5 Formation of hemiacetals and hemiketals. An aldehyde or ketone can react with an alcohol in a 1:1 ratio to yield a hemiacetal or hemiketal, respectively, creating a new chiral center at the carbonyl carbon. Substitution of a second alcohol molecule produces an acetal or ketal. When the second alcohol is part of another sugar molecule, the bond produced is a glycosidic bond (p. 245). istry of ring forms of monosaccharides. However, the six-membered pyranose ring is not planar, as Haworth perspectives suggest, but tends to assume either of two “chair” conformations (Fig. 7–8). Recall from Chapter 1 (p. 19) that two conformations of a molecule are interconvertible without the breakage of covalent bonds, R3 O HO C Ketal R1 C OR4 R 1 H Aldehyde Hemiketal R2 HO C H OH R 1 OR3 Hemiacetal OR3 R2 R 1 C O R2 Alcohol H2O C H2O OH R1 OR2 Ketone Alcohol C H Acetal OR3 OR2 HO R4 R2 R1 HO R4 HO R3 HO R3 group along the chain. The formation of these ring structures is the result of a general reaction between alcohols and aldehydes or ketones to form derivatives called hemiacetals or hemiketals (Fig. 7–5), which contain an additional asymmetric carbon atom and thus can exist in two stereoisomeric forms. For example, D-glucose exists in solution as an intramolecular hemiacetal in which the free hydroxyl group at C-5 has reacted with the aldehydic C-1, rendering the latter carbon asymmetric and producing two stereoisomers, designated and (Fig. 7–6). These six-membered ring compounds are called pyranoses because they resemble the sixmembered ring compound pyran (Fig. 7–7). The systematic names for the two ring forms of D-glucose are -D-glucopyranose and -D-glucopyranose. Aldohexoses also exist in cyclic forms having fivemembered rings, which, because they resemble the fivemembered ring compound furan, are called furanoses. However, the six-membered aldopyranose ring is much more stable than the aldofuranose ring and predominates in aldohexose solutions. Only aldoses having five or more carbon atoms can form pyranose rings. Isomeric forms of monosaccharides that differ only in their configuration about the hemiacetal or hemiketal carbon atom are called anomers. The hemiacetal (or carbonyl) carbon atom is called the anomeric carbon. The and anomers of D-glucose interconvert in aqueous solution by a process called mutarotation. Thus, a solution of -D-glucose and a solution of -D-glucose eventually form identical equilibrium mixtures having identical optical properties. This mixture consists of about one-third -D-glucose, two-thirds -D-glucose, and very small amounts of the linear and five-membered ring (glucofuranose) forms. Ketohexoses also occur in and anomeric forms. In these compounds the hydroxyl group at C-5 (or C-6) reacts with the keto group at C-2, forming a furanose (or pyranose) ring containing a hemiketal linkage (Fig. 7–5). D-Fructose readily forms the furanose ring (Fig. 7–7); the more common anomer of this sugar in combined forms or in derivatives is -D-fructofuranose. Haworth perspective formulas like those in Figure 7–7 are commonly used to show the stereochem- 8885d_c07_238-272 11/21/03 7:38 AM Page 242 Mac113 mac113:122_EDL: