Baixe Carey - Organic Chemistry - chapt25 e outras Notas de estudo em PDF para Química, somente na Docsity! CHAPTER 25 CARBOHYDRATES 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 C,(H,0),, 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 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. Ta major classes of organic compounds common to living systems are lipids, pro- 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 *”sugar” is a combination of the Sanskrit words su (sweet) and gar (sand). Thus, its literal meaning is “sweet 972 sand.” Back| 252 Fischer Projections and D+ Notation (CsH,>06), 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. Sucrose (C,5H55011) + H50 — glucose (CoH,506) + fructose (CH ,506) 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. Celulose 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 Kketoses. 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 p-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 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 of glyceraldehyde have the signs of rotation and absolute configurations shown in Fig- ure 25.1. Two stereochemical descriptors were defined: D and L. The absolute configu- ration of (+)-glyceraldehyde, as depicted in the figure, was said to be D and that of its enantiomer, (—)-glyceraldehyde, 1. Compounds that had a spatial arrangement of sub- stituents analogous to D-(+)- and L(—)-glyceraldehyde were said to have the D and L configurations, respectively. PEN: =PAAA] Some Classes of Monosaccharides Number of carbon atoms Aldose Ketose Four Aldotetrose Ketotetrose Five Aldopentose Ketopentose Six Aldohexose Ketohexose Seven Aldoheptose Ketoheptose Eight Aldooctose Ketooctose Forward Main Menul Toe] Study Guide TOC Student OLC MHHE Website 973 Fischer determined the struc- ture of glucose in 1900 and won the Nobel Prize in chemistry in 1902. Adopting the enantiomers of glyceraldehyde as stereo- chemical reference com- pounds originated with proposals made in 1906 by M. A. Rosanoff, a chemist at New York University. 976 CHAPTER TWENTYFIVE Carbohydrates 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 set 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 p-(+)-glyceraldehyde. PROBLEM 25.3 1-(+)-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. Cellulose is more abundant The aldohexoses include some or 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- stereogenic centers, 16 stereoisomeric aldohexoses are possible; 8 belong to the D series charide composed of Khousands of glucose units and 8 to the L series. All are known, either as naturally Occurring substances or as the (Section 25.15). Methane products of synthesis. The eight D-aldohexoses are given in Figure 25.2; it is the spatial may also be more abundant, arrangement at €-5, hydrogen to the left in a Fischer projection and hydroxyl to the right, but most of the methane comes from glucose. that identifies them as carbohydrates of the D series. PROBLEM 25.4 Name the following sugar: cHO H——OH H——0OH H——0OH HO——H CH>0H 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. E Forward Main Menul Toe] Study Guide TOC) Student OLC| MHHE Website CHO H oH CH,0H D-(+)-Glyceraldehyde CcHO CcHO H 0H HO H H OH H OH CH,0H CH,0H D(—)-Erythrose D(—)-Threose CcHO CcHO CcHO CHO H OH HO H H OH HO H H OH H OH HO H HO H H OH H OH H OH H OH CH,0H CH,0H CcH,0H CH,0H D(—)Ribose D-(—)-Arabinose D(+)-Xylose D(-)-Lyxose CHO CHO CHO CHO CHO CHO CHO cHO H OH HO H H OH HO H H OH HO H H OH HO H H OH H OH HO H HO H H OH H OH HO H HO H H OH H OH H OH H OH HO H HO H HO H HO H H OH H OH H OH H OH H OH H OH H OH H OH CH,0H cH,0H CH,0H CH,0H CH,0H CH,0H CH,0H CH,0H D-(+)-Allose D+(+)-Altrose D(+)Glucose D“(+)Mannose D(—)-Gulose D-(-)Idose D-(+)-Galactose D-(+)-Talose 238887 dêsasc “Ss Em 28 “2 3 q 220 isso sido: Back Forward] MainMenu) TOC] StudyGuide TOC] Student OLC| | MHHE Website vs sasoxayopIv pue sasojuadop|y LL6 978 CHAPTER TWENTYFIVE Carbohydrates L(—)-Galactose also occurs naturally and can be prepared by hydrolysis of flaxseed gum and agar. The principal source of D-(+)-mannose is hydrolysis of the polysaccharide of the ivory nut, a large, nut-like seed obtained from a South American palm. 25.5 A MNEMONIC FOR CARBOHYDRATE CONFIGURATIONS See, for example, the No- The task of relating carbohydrate configurations to names requires either a world-class vember 1955 issue of the memory or an easily recalled mnemonic. A mnemonic that serves us well here was pop- Pao e da aa ularized by the husband-wife team of Louis F. Fieser and Mary Fieser of Harvard Uni- ion (p. 584). An article giv- os - — . E er afteferences to a varieiffi versity in their 1956 textbook, Organic Chemistry. As with many mnemonics, it's not chemistry mnemonics ap- clear who actually invented it, and references to this particular one appeared in the chem- pears in the July 1960 issue” ical education literature before publication of the Fiesers” text. The mnemonic has two of the Journal of Chemical f (1 f ing d th - - Idoh in a losical Education (p. 366). 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. A systematic way to set down all the D-hexoses (as in Fig. 25.2) is to draw skele- tons 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 D series. Working up the car- bon 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 result- ing 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. (RAXL is an easily remem- bered nonsense word that gives the correct sequence.) This pattern is discernible even in the aldotetroses erythrose and threose. 25.6 CYCLIC FORMS OF CARBOHYDRATES: FURANOSE FORMS Aldoses incorporate two functional groups, C=O and OH, which are capable of react- ing 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 hemiacetal results, 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 pyranose forms. The ring carbon that is derived from the carbonyl group, the one that bears two oxygen substituents, is called the anomerie carbon. Aldoses exist almost exclusively as their cyclic hemiacetals; very little of the open- chain form is present at equilibrium. To understand their structures and chemical reac- tions, 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 stereo- genic center. E Forward Main Menul Toe] Study Guide TOC) Student OLC| MHHE Website Back| 257 — Cyclic Forms of Carbohydrates: Pyranose Forms 981 As viewed in the drawing, a 120º anticlockwise rotation of C-4 places its hydroxyl group in the proper position. At the same time, this rotation moves the CH,0H group to a posi- tion such that it will become a substituent that is “up” on the five-membered ring. The hydrogen at C-4 then will be “down” in the furanose form. HOCH, HOCH, B-D-Ribofuranose a-D-Ribofuranose PROBLEM 25.5 Write Haworth formulas corresponding to the furanose forms of each of the following carbohydrates: (a) D-Xylose (c) 1-Arabinose (b) D-Arabinose (d) pThreose SAMPLE SOLUTION (a) The Fischer projection of D-xylose is given in Figure 25.2. cHO — 5 H OH H CHO0H HO——H 4 cH=0 OH H/ H——oH HO q, CH,;0H H OH D-Xylose Ediipsed conformation of D-xylose Carbon-4 of D-xylose must be rotated in an anticlockwise sense in order to bring its hydroxyl group into the proper orientation for furanose ring formation. H E 5 rotate about “ H CH0H Ce ca) HOCH> 70, HOCH> HOCH> bond a a cH=0 5 cH=0 — HOXOH H/ ' HNOH H/y HNOH H/0H =, H OH H OH D-Xylose P-D-Xylofuranose a-D-Xylofuranose | 25.7 CYCLIC FORMS OF CARBOHYDRATES: PYRANOSE FORMS During the discussion of hemiacetal formation in D-ribose in the preceding section, you may have noticed that aldopentoses have the potential of forming a six-membered cyclic hemiacetal via addition of the C-5 hydroxyl to the carbonyl group. This mode of ring closure leads to a- and B-pyranose forms: Forward Main Menul Toe] Study Guide TOC Student OLC MHHE Website 982 CHAPTER TWENTYFIVE Carbohydrates cHO H——oH H——0H Pyranose ring formation H—[—0H involves this du “É hydroxyl group 20] Eclipsed conformation of D-Ribose p-ribose H HO B-D-Ribopyranose a-D-Ribopyranose Like aldopentoses, aldohexoses such as D-glucose are capable of forming two fura- nose forms (a and B) and two pyranose forms (a and B). The Haworth representations of the pyranose forms of D-glucose are constructed as shown in Figure 25.4; each has a CH,0H group as a substituent on the six-membered ring. Haworth formulas are satisfactory for representing configurational relationships in pyranose forms but are uninformative as to carbohydrate conformations. X-ray crystal- lographic studies of a large number of carbohydrates reveal that the six-membered pyra- nose ring of D-glucose adopts a chair conformation: HOCH, Make a molecular model 2) of the chair conformation of H B-o-glucopyranose. HONCH H HOCH, H HONCH H a-p-Glucopyranose All the ring substituents other than hydrogen in B-D-glucopyranose are equatorial in the most stable chair conformation. Only the anomeric hydroxyl group is axial in the a iso- mer; all the other substituents are equatorial. Other aldohexoses behave similarly in adopting chair conformations that permit the CH,0H substituent to occupy an equatorial orientation. Normally the CH,50H group is the bulkiest, most conformationally demanding substituent in the pyranose form of a hexose. Back| Forward Main Menul Toe] Study Guide TOC Student OLC MHHE Website 257 — Cyclic Forms of Carbohydrates: Pyranose Forms 983 CH,0H 5 D-Glucose (hydroxyl group at CS is involved in pyranose ring formation) Eclipsed conformation of D-Glucose; hydroxyl at C-S is not properly oriented for ring formation bond in anticlockwise rotate about C4-C-5 direction HOCH, H A oH H HoNQH H/ oH HoNH H/0n HOCH, H AH H oH B-D-Glucopyranose a-D-Glucopyranose Eclipsed conformation of D-glucose in proper orientation for pyranose ring formation PROBLEM 25.6 Clearly represent the most stable conformation of the B-pyra- nose form of each of the following sugars: (a) D-Galactose (c) 1-Mannose (b) Dp-Mannose (d) 1-Ribose SAMPLE SOLUTION (a) By analogy with the procedure outlined for p-glucose in Figure 25.4, first generate a Haworth formula for B-D-galactopyranose: cHO nom H con HOCH> HO 2 HO OH HO —H OH on n/$TO OH H HO——H Hj Hj H H——oOH H 0H H OH CH,;0H D-Galactose B-D-Galactopyranose (Haworth formula) Next, redraw the planar Haworth formula more realistically as a chair conforma- tion, choosing the one that has the CH>0H group equatorial. Forward Main Menul Toe] Study Guide TOC Student OLC FIGURE 25.4 Haworth for- mulas for «- and B-pyranose forms of p-glucose. MHHE Website 986 CHAPTER TWENTYFIVE Carbohydrates operate in different directions but are comparable in magnitude in aqueous solution, the a-pyranose form is more abundant for some carbohydrates and the B-pyranose form for others. 25.9 KETOSES Up to this point all our attention has been directed toward aldoses, carbohydrates hav- ing an aldehyde function in their open-chain form. Aldoses are more common than ketoses, and their role in biological processes has been more thoroughly studied. Nev- ertheless, a large number of ketoses are known, and several of them are pivotal inter- mediates in carbohydrate biosynthesis and metabolism. Examples of some ketoses include D-ribulose, L-xylulose, and D-fructose: OH OH OH c=o c=o c=o H——oH H——0H HOo—H H——oH HO——H H——0H CH,0H CH,0H H——0H CH,0H p-Ribulose L-Xylulose p-Fructose (a 2-ketopentose (a 2-ketopentose (a 2-ketohexose also that is a key excreted inexcessive known as levulose; compound in amounts in theurine itis found in honey photosynthesis) of persons afflicted and is signficantIy with the mild genetic sweeter than table disorder pentosuria) sugar) mM these three examples the carbonyl group is located at C-2, which is the most com- mon location for the carbonyl function in naturally occurring ketoses. [poem 25.8 How many ketotetroses are possible? Write Fischer projcios] for each. Ketoses, like aldoses, exist mainly as cyclic hemiacetals. In the case of D-ribulose, furanose forms result from addition of the C-5 hydroxyl to the carbonyl group. Í H Ou OH O oH O cHoH A — + NT H/ So HE H/cH,0H E H/0H HO OH HO OH HO OH Eclipsed conformation of B-D-Ribulofuranose a-D-Ribulofuranose p-ribulose E Forward Main Menul Toe] Study Guide TOC) Student OLC| MHHE Website Back| 25.10 Deoxy Sugars The anomeric carbon of a furanose or pyranose form of a ketose bears both a hydroxyl group and a carbon substituent. In the case of 2-ketoses, this substituent is a CH,OH group. As with aldoses, the anomeric carbon of a cyclic hemiacetal is readily identifi- able because it is bonded to two oxygens. 25.10 DEOXY SUGARS A commonplace variation on the general pattern seen in carbohydrate structure is the replacement of one or more of the hydroxyl substituents by some other atom or group. m deoxy sugars the hydroxyl group is replaced by hydrogen. Two examples of deoxy sugars are 2-deoxy-D-ribose and L-rhamnose: cHO HH H—oH H—oH cH,0H 2-Deoxy-p-ribose cHO H— 0H H—0H HO—H HO —H CH; L-Rhamnose (6-deoxy-L-mannose) The hydroxyl at C-2 in p-ribose is absent in 2-deoxy-D-ribose. In Chapter 27 we shall see how derivatives of 2-deoxy-D-ribose, called deoxyribonucleotides, are the funda- mental building blocks of deoxyribonucleic acid (DNA), the material responsible for stor- ing genetic information. L-Rhamnose is a compound isolated from a number of plants. Its carbon chain terminates in a methyl rather than a CH,0H group. PROBLEM 25.9 Write Fischer projections of (a) Cordycepose (3-deoxy-p-ribose): a deoxy sugar isolated by hydrolysis of the antibiotic substance cordycepin (b) L-Fucose (6-deoxy-L-galactose): obtained from seaweed SAMPLE SOLUTION (a) The hydroxyl group at C-3 in p-ribose is replaced by hydrogen in 3-deoxy-p-ribose. cHOo cHOo H oH H OH H oH H H H oH H OH CH,0H CH,0H p-Ribose 3-Deoxy-b-ribose (from Figure 25.2) (cordycepose) Forward Main Menul Toe] Study Guide TOC Student OLC 987 MHHE Website 988 CHAPTER TWENTYFIVE Carbohydrates 25.11 AMINO SUGARS Another structural variation is the replacement of a hydroxyl group in a carbohydrate by For a review of the isolation of chitin from natural an amino group to give an amino sugar. The most abundant amino sugar is one of the sources and some of its uses, oldest and most abundant organic compounds on earth. N-Acetyl-D-glucosamine is the see the November 1990 issue : a o pis Erthe Journal of Chemical main component of the polysaccharide in chitin, the substance that makes up the tough Education (pp. 938-942). outer skeleton of arthropods and insects. Chitin has been isolated from a 25-million-year- old beetle fossil, and more than 10”! tons of chitin is produced in the biosphere each year. Lobster shells, for example, are mainly chitin. More than 60 amino sugars are known, many of them having been isolated and identified only recently as components of antibiotics. The anticancer drug doxorubicin hydrochloride (Adriamycin), for exam- ple, contains the amino sugar L-daunosamine as one of its structural units. HOCH, OH HO HO on H€ o H HNCCH, | NH, o HO N-Acetyl-D-glucosamine L-Daunosamine 25.12 BRANCHED-CHAIN CARBOHYDRATES Carbohydrates that have a carbon substituent attached to the main chain are said to have a branched chain. D-Apiose and L-vancosamine are representative branched-chain carbohydrates: CcHO cu, 9H H-—[—0H Branching H; -0 H HO—-—cH,0H | Soup NA NH, CH,0H HO D-Apiose L-Vancosamine D-Apiose can be isolated from parsley and is a component of the cell wall polysaccha- ride of various marine plants. Among its novel structural features is the presence of only a single stereogenic center. L-Vancosamine is but one portion of vancomycin, a powerful antibiotic that is reserved for treating only the most stubborn infections. L-Vancosamine is not only a branched-chain carbohydrate, it is a deoxy sugar and an amino sugar as well. 25.13 GLYCOSIDES Glycosides are a large and very important class of carbohydrate derivatives character- ized by the replacement of the anomeric hydroxyl group by some other substituent. Gly- cosides are termed O-glycosides, N-glycosides, S-glycosides, and so on, according to the atom attached to the anomeric carbon. E Forward Main Menul Toe] Study Guide TOC) Student OLC| MHHE Website 25.14 — Disaccharides 991 All of the reactions, from D-glucose to the methyl glycosides via the carbocation, are reversible. The overall reaction is thermodynamically controlled and gives the same mixture of glycosides irrespective of which stereoisomeric pyranose form of D-glucose we start with. Nor does it matter whether we start with a pyranose form or a furanose form of D-glucose. Glucopyranosides are more stable than glucofuranosides and pre- dominate at equilibrium. PROBLEM 25.11 Methyl glycosides of 2-deoxy sugars have been prepared by the acid-catalyzed addition of methanol to unsaturated sugars known as glycals. HO HO HO HOCH,> HOCH, HOCH, 9, CHz0H 9, 4 9 HO 2=p ta HO H HO OCH; OCH; H Galactal Methyl 2-deoxy-a-D- Methyl 2-deoxy-p-D- Iyxohexopyranoside Iyxohexopyranoside (38%) (36%) Suggest a reasonable mechanism for this reaction. ] Under neutral or basic conditions glycosides are configurationally stable; unlike the free sugars from which they are derived, glycosides do not exhibit mutarotation. Con- verting the anomeric hydroxyl group to an ether function (hemiacetal > acetal) prevents its reversion to the open-chain form in neutral or basic media. In aqueous acid, acetal formation can be reversed and the glycoside hydrolyzed to an alcohol and the free sugar. 25.14 DISACCHARIDES Disaccharides are carbohydrates that yield two monosaccharide molecules on hydroly- sis. Structurally, disaccharides are glycosides in which the alkoxy group attached to the anomeric carbon is derived from a second sugar molecule. Maltose, obtained by the hydrolysis of starch, and cellobiose, by the hydrolysis of cellulose, are isomeric disaccharides. In both maltose and cellobiose two D-glucopyra- nose units are joined by a glycosidic bond between C-1 of one unit and C-4 of the other. The two are diastereomers, differing only in the stereochemistry at the anomeric carbon of the glycoside bond; maltose is an a-glycoside, cellobiose is a B-glycoside. HOCH, HOCH, Maltose: (at) tm O: can view molecular models of maltose and cello- Cellobiose: () — biose on Learning By Modeling. The stereochemistry and points of connection of glycosidic bonds are commonly designated by symbols such as a(1,4) for maltose and B(1,4) for cellobiose; a and B designate the stereochemistry at the anomeric position; the numerals specify the ring car- bons involved. E Forward Main Menul Toe] Study Guide TOC) Student OLC| MHHE Website 992 CHAPTER TWENTYFIVE Carbohydrates : Both maltose and cellobiose have a free anomeric hydroxyl group that is not The free anomeric hydroxyl . : é Í - - À group is the one shown at involved in a glycoside bond. The configuration at the free anomeric center is variable the far right of the preceding and may be either a or B. Indeed, two stereoisomeric forms of maltose have been iso- Peseural formula. The omg lated: one has its anomeric hydroxyl group in an equatorial orientation; the other has an bol «vm is used to represent : , a bond of variable stereo- axial anomeric hydroxyl. chemistry. PROBLEM 25.12 The two stereoisomeric forms of maltose just mentioned undergo mutarotation when dissolved in water. What is the structure of the key intermediate in this process? The single difference in their structures, the stereochemistry of the glycosidic bond, causes maltose and cellobiose to differ significantly in their three-dimensional shape, as the molecular models of Figure 25.6 illustrate. This difference in shape affects the way in which maltose and cellobiose interact with other chiral molecules such as proteins, and they behave much differently toward enzyme-catalyzed hydrolysis. An enzyme known as maltase catalyzes the hydrolytic cleavage of the a-glycosidic bond of maltose but is without effect in promoting the hydrolysis of the B-glycosidic bond of cellobiose. A different enzyme, emulsin, produces the opposite result: emulsin catalyzes the hydrol- ysis of cellobiose but not of maltose. The behavior of each enzyme is general for glu- cosides (glycosides of glucose). Maltase catalyzes the hydrolysis of a-glucosides and is Maltose FIGURE 25.6 Molecu- É 1 lar models of the disaccha- rides maltose and cellobiose. Two p-glucopyranose units are connected by a glycoside linkage between C-1 and C-4. The glycosidic bond has the a orientation in maltose and is B in cellobiose. Maltose and cellobiose are diastereomers. Cellobiose E Forward Main Menul Toe] Study Guide TOC) Student OLC| MHHE Website Back| 2515 Polysaccharides D-Glucose portion of me D-Fructose portion / molecule => HocH, CH,0H a-Glycoside tora 7 to anomerie eta 7 of D-glucose DD dom B-Glycoside bond to anomeric position of D-fructose also known as e-glucosidase, whereas emulsin catalyzes the hydrolysis of B-glucosides and is known as B-glucosidase. The specificity of these enzymes offers a useful tool for structure determination because it allows the stereochemistry of glycosidic linkages to be assigned. Lactose is a disaccharide constituting 2-6% of milk and is known as milk sugar. It differs from maltose and cellobiose in that only one of its monosaccharide units is D-glucose. The other monosaccharide unit, the one that contributes its anomeric carbon to the glycoside bond, is D-galactose. Like cellobiose, lactose is a B-glycoside. Cellobiose: ut Lactose: =— Digestion of lactose is facilitated by the B-glycosidase lactase. A deficiency of this enzyme makes it difficult to digest lactose and causes abdominal discomfort. Lactose intolerance is a genetic trait, it is treatable through over-the-counter formulations of lac- tase and by limiting the amount of milk in the diet. The most familiar of all the carbohydrates is sucrose—common table sugar. Sucrose is a disaccharide in which D-glucose and D-fructose are joined at their anomeric carbons by a glycosidic bond (Figure 25.7). Its chemical composition is the same irrespective of its source; sucrose from cane and sucrose from sugar beets are chemi- cally identical. Since sucrose does not have a free anomeric hydroxyl group, it does not undergo mutarotation. 25.15 POLYSACCHARIDES Cellulose is the principal structural component of vegetable matter. Wood is 30-40% cel- lulose, cotton over 90%. Photosynthesis in plants is responsible for the formation of 10º tons per year of cellulose. Structurally, cellulose is a polysaccharide composed of sev- eral thousand D-glucose units joined by B(1,4)-glycosidic linkages (Figure 25.8). Com- plete hydrolysis of all the glycosidic bonds of cellulose yields D-glucose. The disac- charide fraction that results from partial hydrolysis is cellobiose. Forward Main Menul Toe] Study Guide TOC Student OLC 993 Da 25.7 The structure of sucrose. O can view molecular models of cellobiose and lactose on Learning By Modeling. MHHE Website 996 FIGURE 25.11 Terminal car- bohydrate units of human blood-group glycoproteins. difference between the type A, type B, and type O glycoproteins lies in the group designated R. The structural The classical approach to structure determination in carbohydrate chemistry is best exemplified by Fischer's work with D-glucose. A de- tailed account of this study appears in the August 1941 issue of the Journal of Chem- ical Education (pp. 353-357). E Forward CHAPTER TWENTYFIVE Carbohydrates HO cH,0H o R-O o— Da ooo | Dm o H;C o oH HO HO HO HO cH,0H cH,0H o, o, HO HO no CHE oH o R R R Type A Type B Type O 25.17 CARBOHYDRATE STRUCTURE DETERMINATION Present-day techniques for structure determination in carbohydrate chemistry are sub- stantially the same as those for any other type of compound. The full range of modern instrumental methods, including mass spectrometry and infrared and nuclear magnetic resonance spectroscopy, is brought to bear on the problem. If the unknown substance is crystalline, X-ray diffraction can provide precise structural information that in the best cases is equivalent to taking a three-dimensional photograph of the molecule. Before the widespread availability of instrumental methods, the major approach to structure determination relied on a battery of chemical reactions and tests. The response of an unknown substance to various reagents and procedures provided a body of data from which the structure could be deduced. Some of these procedures are still used to supplement the information obtained by instrumental methods. To better understand the scope and limitations of these tests, a brief survey of the chemical reactions of carbo- hydrates is in order. In many cases these reactions are simply applications of chemistry you have already learned. Certain of the transformations, however, are unique to carbo- hydrates. 25.18 REDUCTION OF CARBOHYDRATES Although carbohydrates exist almost entirely as cyclic hemiacetals in aqueous solution, they are in rapid equilibrium with their open-chain forms, and most of the reagents that react with simple aldehydes and ketones react in an analogous way with the carbonyl functional groups of carbohydrates. The carbonyl group of carbohydrates can be reduced to an alcohol function. Typi- cal procedures include catalytic hydrogenation and sodium borohydride reduction. Lithium aluminum hydride is not suitable, because it is not compatible with the solvents (water, Main Menul Toe] Study Guide TOC Student OLC MHHE Website ow sweet is it? There is no shortage of compounds, nat- ural or synthetic, that taste sweet. The most familiar are naturally occurring sugars, especially su- crose, glucose, and fructose. All occur naturally, with Among sucrose, glucose, and fructose, fructose is the sweetest. Honey is sweeter than table sugar because it contains fructose formed by the isomerization of glucose as shown in the equation. You may have noticed that most soft drinks con- tain “high-fructose corn syrup.” Corn starch is hy- drolyzed to glucose, which is then treated with glu- cose isomerase to produce a fructose-rich mixture. The CH=0 Ra H——OH C=0 Glucose HO——H | isomerase HO——H Starch + H)0 — —— H——0OH H——0OH H——0OH H——0OH CH,0H CH,0H D-(+)-Glucose 25.18 Reduction of Carbohydrates 997 worldwide production of sucrose from cane and sugar beets exceeding 100 million tons per year. Glu- cose is prepared by the enzymatic hydrolysis of starch, and fructose is made by the isomerization of glucose. D(—)-Fructose enhanced sweetness permits less to be used, reducing the cost of production. Using less carbohydrate-based sweetener also reduces the number of calories. Artificial sweeteners are a billion-dollar-per- year industry. The primary goal is, of course, to maxi- mize sweetness and minimize calories. We'll look at the following three sweeteners to give us an over- view of the field. cl HOCH> o HO o HO H nal NH OH oH H;NCHCNHCHCH, SO, 9 o cH>cl OCCH> Gota CICH, o Saccharin sucralose Aspartame All three ofthese are hundreds of times sweeter than applications were not in weight control, but as a sucrose and variously described as “low-calorie” or replacement for sugar in the diet of diabetics before “nonnutritive” sweeteners. insulin became widely available. Saccharin was discovered at Johns Hopkins Uni- Sucralose has the structure most similar to su- versity in 1879 in the course of research on coal-tar crose. Galactose replaces the glucose unit of sucrose, derivatives and is the oldest artificial sweetener. In and chlorines replace three of the hydroxyl groups. spite of its name, which comes from the Latin word Sucralose is the newest artificial sweetener, having for sugar, saccharin bears no structural relationship been approved by the U.S. Food and Drug Adminis- to any sugar. Nor is saccharin itself very solublein wa- | tration in 1998. The three chlorine substituents do ter. The proton bonded to nitrogen, however, is fairly not diminish sweetness, but do interfere with the acidic and saccharin is normally marketed as its ability of the body to metabolize sucralose. It, there- water-soluble sodium or calcium salt. Its earliest fore, has no food value and is “noncaloric.” —Cont. E Forward Main Menul Toe] Study Guide TOC) Student OLC| MHHE Website 998 CHAPTER TWENTYFIVE Carbohydrates Aspartame is the market leader among artifi- Saccharin, sucralose, and aspartame illustrate cial sweeteners. Itis a methyl ester of a dipeptide, un- the diversity of structural types that taste sweet, and related to any carbohydrate. It was discovered in the the vitality and continuing development of the in- course of research directed toward developing drugs dustry of which they are a part.* to relieve indigestion. *For more information, including theories of structure-taste relationships, see the symposium “Sweeteners and Sweetness Theory” in the Au- gust, 1995 issue of the Journal of Chemical Education, pp. 671-683. alcohols) that are required to dissolve carbohydrates. The products of carbohydrate reduc- tion are called alditols. Since these alditols lack a carbonyl group, they are, of course, incapable of forming cyclic hemiacetals and exist exclusively in noncyclic forms. CHO CH,0H H—— OH H——0OH a-D-Galactofuranose, or B-p-Galactofuranose, or HO——H uu, HO—f—H a-D-Galactopyranose, or Ho——g “º go B-D-Galactopyranose H——0OH H——0OH CH,0H CH,0H p-Galactose D-Galactitol (90%) PROBLEM 25.13 Does sodium borohydride reduction of p-ribose yield an opti- cally active product? Explain. Another name for glucitol, obtained by reduction of D-glucose, is sorbitol; it is used as a sweetener, especially in special diets required to be low in sugar. Reduction of D-fructose yields a mixture of glucitol and mannitol, corresponding to the two possi- ble configurations at the newly generated stereogenic center at C-2. 25.19 OXIDATION OF CARBOHYDRATES A characteristic property of an aldehyde function is its sensitivity to oxidation. A solu- tion of copper(II) sulfate as its citrate complex (Benedict's reagent) is capable of oxi- dizing aliphatic aldehydes to the corresponding carboxylic acid. f í RCH + 2Cu?* + 5HO” —>» RCO” + CuO + 3H,0 Aldehyde - Fromcopper(ID) — Hydroxide Carboxylate Copper(l) Water sulfate ion anion oxide The formation of a red precipitate of copper(I) oxide by reduction of Cu(II) is taken as nn a positive test for an aldehyde. Carbohydrates that give positive tests with Benedict's Benedict's reagent is the key material in a test kit avail- Teagent are termed reducing sugars. able from drugstores that Aldoses are reducing sugars, since they possess an aldehyde function in their open- [aSgn e individuals tomo chain form. Ketoses are also reducing sugars. Under the conditions of the test, ketoses tor the glucose levels in their a : o - ai Eine equilibrate with aldoses by way of enediol intermediates, and the aldoses are oxidized by the reagent. Back| Forward Main Menul Toe] Study Guide TOC Student OLC MHHE Website Back| 25.20 Cyanohydrin Formation and Carbohydrate Chain Extension 1001 Uronic acids are biosynthetic intermediates in various metabolic processes; ascorbic acid (vitamin C), for example, is biosynthesized by way of glucuronic acid. Many metabolic waste products are excreted in the urine as their glucuronate salts. 25.20 CYANOHYDRIN FORMATION AND CARBOHYDRATE CHAIN EXTENSION The presence of an aldehyde function in their open-chain forms makes aldoses reactive toward nucleophilic addition of hydrogen cyanide. Addition yields a mixture of diastereo- meric cyanohydrins. CN CN CHO H oH HO H a-L-Arabinofuranose, or B-L-Arabinofuranose, or H-——0H gx, H OH 4 H OH a-L-Arabinopyranose, or HO——H HO H HO H B-L-Arabinopyranose HO——H HO H HO H CH,0H CcH,0H CH,0H L-Arabinose L-Mannononitrile L-Glucononitrile The reaction is used for the chain extension of aldoses in the synthesis of new or unusual sugars. In this case, the starting material, L-arabinose, is an abundant natural product and possesses the correct configurations at its three stereogenic centers for elaboration to the relatively rare L-enantiomers of glucose and mannose. After cyanohydrin formation, the cyano groups are converted to aldehyde functions by hydrogenation in aqueous solution. Under these conditions, —C=N is reduced to —CH=NH and hydrolyzes rapidly to —CH=0. Use of a poisoned palladium-on-barium sulfate catalyst prevents further reduction to the alditols. CN cHO H——oH H—— 0H H—0H vo. H——0H HO-—H Pd/BaSO, HO—H HO—H HO—H cH,0H cH,0H L-Mannononitrile L-Mamose (569% yield from L-arabinose) (Similarly, L-glucononitrile has been reduced to L-glucose; its yield was 26% from L-arabinose.) An older version of this sequence is called the Kiliani-Fischer synthesis. It, too, proceeds through a cyanohydrin, but it uses a less efficient method for converting the cyano group to the required aldehyde. Forward Main Menul Toe] Study Guide TOC Student OLC MHHE Website 1002 CHAPTER TWENTYFIVE Carbohydrates 25.21 EPIMERIZATION, ISOMERIZATION, AND RETRO-ALDOL CLEAVAGE REACTIONS OF CARBOHYDRATES Carbohydrates undergo a number of isomerization and degradation reactions under both laboratory and physiological conditions. For example, a mixture of glucose, fructose, and mannose results when any one of them is treated with aqueous base. This reaction can be understood by examining the consequences of enolization of glucose: çHo quom qro H—C—oH c—oH HO—C—H HO H o no HODH o muo HO—H H——0H H——0H H——0H H—0H H—0H H——0H cH,0H cH,0H cH,0H p-Glucose Enediol D-Mannose (R configuration (C-2 not a stereogenic (S configuration atC2) center) atC2) Because the configuration at C-2 is lost on enolization, the enediol intermediate can revert either to D-glucose or to D-mannose. Two stereoisomers that have multiple stereo- genic centers but differ in configuration at only one of them are referred to as epimers. Glucose and mannose are epimeric at C-2. Under these conditions epimerization occurs only at C-2 because it alone is « to the carbonyl group. There is another reaction available to the enediol intermediate. Proton transfer from water to C-1 converts the enediol not to an aldose but to the Ketose D-fructose: See the boxed essay “How CHOH CH,0H Sweet It Is!” for more on this | process. Cc—oH C=0 D-Glucose or Ho .0, HO——"H no no, HO——H D-Mannose H——oH H——oH H——0OH H——0OH CH,0H CcH,0H Enediol D-Fructose The isomerization of D-glucose to D-fructose by way of an enediol intermediate is an important step in glycolysis, a complex process (11 steps) by which an organism con- verts glucose to chemical energy. The substrate is not glucose itself but its 6-phosphate ester. The enzyme that catalyzes the isomerization is called phosphoglucose isomerase. E Forward Main Menul Toe] Study Guide TOC) Student OLC| MHHE Website 25.21 Epimerization, Isomerization, and Retro-Aldol Cleavage Reactions of Carbohydrates Es Ee o H—C—oH CoH I HO—H HO—H (HO),POCH, HO O = H oH == H oH = HO. Si H——oH H——oH 0H CHORO, CHORO, 0 0 D-Glucose Open-chain form of Enediol 6-phosphate p-glucose 6-phosphate Com c=o HOH H——oH H——oH CHONOM, Open-chain form of p-Fructose 6-phosphate Following its formation, D-fructose 6-phosphate is converted to its corresponding 1,6-phosphate diester, which is then cleaved to two 3-carbon fragments under the influ- ence of the enzyme aldolase: I CH,OP(0H) CH,OP(OH), c=o d— o HO —H Catia, Dogs H—— 0H To çH>o H——0H u-d—ou CH,OP(OH), dmorom, ó b p-Fructose 1,6-diphosphate Dihydroxyacetone phosphate p-Glyceraldehyde 3-phosphate This cleavage is a retro-aldol reaction. It is the reverse of the process by which D-fruc- tose 1,6-diphosphate would be formed by addition of the enolate of dihydroxyacetone phosphate to D-glyceraldehyde 3-phosphate. The enzyme aldolase catalyzes both the E Forward Main Menul Toe] Study Guide TOC Student OLC 1003 o | CH;OP(OH)» O cHoH HNI HO/6H oH H p-Fructose 6-phosphate MHHE Website 1006 CHAPTER TWENTYFIVE Carbohydrates The use of periodic acid oxidation in structure determination can be illustrated by a case in which a previously unknown methyl glycoside was obtained by the reaction of D-arabinose with methanol and hydrogen chloride. The size of the ring was identified as five-membered because only one mole of periodic acid was consumed per mole of gly- coside and no formic acid was produced. Were the ring six-membered, two moles of periodic acid would be required per mole of glycoside and one mole of formic acid would be produced. HOCH, O. H HNI |HO/0cH, HO | H Only one site for periodic acid Two sites of periodic acid cleavage in methyl cleavage in methyl a-D-arabinofuranoside a-p-arabinopyranoside, C3 lost as formic acid PROBLEM 25.17 Give the products of periodic acid oxidation of each of the fol- lowing. How many moles of reagent will be consumed per mole of substrate in each case? (a) D-Arabinose (d) CH,0H (b) D-Ribose Ho: H (c) Methyl B-D-glucopyranoside o, OCH; HOH H/y H OH SAMPLE SOLUTION (a) The a-hydroxy aldehyde unit at the end of the sugar chain is cleaved, as well as all the vicinal diol functions. Four moles of periodic acid are required per mole of p-arabinose. Four moles of formic acid and one mole of formaldehyde are produced. cH=0 HCO,H | Formicacid mam D-Arabinose, showing HO—C—H HCO,H | Formicacid points of cleavage by aHio, periodic acid; each H—C—OH —> Hco,H Formic acid cleavage requires one equivalent of HIO4. H—C—oH HCO2H | Formicacid CH,0H H;C=0 — Formaldehyde 25.24 SUMMARY Section 25.1 -Carbohydrates are marvelous molecules! In most of them, every carbon bears a functional group, and the nature of the functional groups changes as the molecule interconverts between open-chain and cyclic hemiacetal E Forward Main Menul Toe] Study Guide TOC) Student OLC| MHHE Website Back| Section 25.2 Section 25.3 Section 25.4 Section 25.5 Sections 25.6-25.7 Forward 25.24 Summary forms. Any approach to understanding carbohydrates must begin with structure. Carbohydrates are polyhydroxy aldehydes and ketones. Those derived from aldehydes are classified as aldoses; those derived from ketones are ketoses. Fischer projections and D-L notation are commonly used to describe car- bohydrate stereochemistry. The standards are the enantiomers of glycer- aldehyde. cHO cHO oH HO H cH,0H cH,0H p-(+)-Glyceraldehyde | 1-(—)-Glyceraldehyde Aldotetroses have two stereogenic centers, so four stereoisomers are pos- sible. They are assigned to the D or the L series according to whether the configuration at their highest numbered stereogenic center is analogous to D- or L-glyceraldehyde, respectively. Both hydroxyl groups are on the same side of the Fischer projection in erythrose, but on opposite sides in threose. The Fischer projections of D-erythrose and D-threose are shown in Figure 25.2. Of the eight stereoisomeric aldopentoses, Figure 25.2 shows the Fischer projections of the D-enantiomers (D-ribose, D-arabinose, D-xylose, and D-lyxose). Likewise, Figure 25.2 gives the Fischer projections of the eight D-aldohexoses. The aldohexoses are allose, altrose, glucose, mannose, gulose, idose, galactose, and talose. The mnemonic “AII altruists gladly make gum in gallon tanks” is helpful in writing the correct Fischer projection for each one. Most carbohydrates exist as cyclic hemiacetals. Cyclic acetals with five- membered rings are called furanose forms; those with six-membered rings are called pyranose forms. HOCH, O | HNT H/0H OH OH a-D-Ribofuranose B-p-Glucopyranose The anomeric carbon in a cyclic acetal is the one attached to two oxy- gens. It is the carbon that corresponds to the carbonyl carbon in the open- chain form. The symbols a and B refer to the configuration at the anomeric carbon. Main Menul Toe] Study Guide TOC Student OLC 1007 MHHE Website 1008 CHAPTER TWENTYFIVE Carbohydrates Section 25.8 A particular carbohydrate can interconvert between furanose and pyra- nose forms and between the a and B configuration of each form. The change from one form to an equilibrium mixture of all the possible hemi- acetals causes a change in optical rotation called mutarotation. Section 25.9 Ketoses are characterized by the ending -ulose in their name. Most naturally occurring ketoses have their carbonyl group located at C-2. Like aldoses, ketoses cyclize to hemiacetals and exist as furanose or pyranose forms. Sections Structurally modified carbohydrates include deoxy sugars, amino 25.10-25.12 | sugars, and branched-chain carbohydrates. Section 25.13 Glycosides are acetals, compounds in which the anomeric hydroxyl group has been replaced by an alkoxy group. Glycosides are easily prepared by allowing a carbohydrate and an alcohol to stand in the presence of an acid catalyst. HOCH, w, HO 9 D-Glucose + ROH — NDA or + HO OH A glycoside Sections Disaccharides are carbohydrates in which two monosaccharides are 25.14-25.15 | joined by a glycoside bond. Polysaccharides have many monosaccharide units connected through glycosidic linkages. Complete hydrolysis of disaccharides and polysaccharides cleaves the glycoside bonds, yielding the free monosaccharide components. Section 25.16 Carbohydrates and proteins that are connected by a chemical bond are called glycoproteins and often occur on the surfaces of cells. They play an important role in the recognition events connected with the immune response. Sections Carbohydrates undergo chemical reactions characteristic of aldehydes and 25.17-25.24 | ketones, alcohols, diols, and other classes of compounds, depending on their structure. A review of the reactions described in this chapter is pre- sented in Table 25.2. Although some of the reactions have synthetic value, many of them are used in analysis and structure determination. PROBLEMS 25.18 Refer to the Fischer projection of D-(+)-xylose in Figure 25.2 (Section 25.4) and give struc- tural formulas for (a) (=) Xylose (Fischer projection) (b) D-Xylitol (e) B-D-Xylopyranose (d) a-L-Xylofuranose (e) Methyl a-L-xylofuranoside (f) D-Xylonic acid (open-chain Fischer projection) (8) -Lactone of D-xylonic acid (h) y-Lactone of D-xylonic acid () D-Xylaric acid (open-chain Fischer projection) Back| Forward Main Menul Toe] Study Guide TOC Student OLC MHHE Website Back| Problems 25.19 From among the carbohydrates shown in Figure 25.2, choose the D-aldohexoses that yield (a) An optically inactive product on reduction with sodium borohydride (b) An optically inactive product on oxidation with bromine (c) An optically inactive product on oxidation with nitric acid (d) The same enediol 25.20 Write the Fischer projection of the open-chain form of each of the following: ou HO HOCH; 7-0 oH 0, a) o (a) oH (e) Hc 0H HO HO 0H CH;0H HorH HOCH: 4 O 0H HO (b) (d) CH,0H HH 0H H H HO 0H HO OH 25.21 What are the R,S configurations of the three stereogenic centers in D-ribose? (A molecular model will be helpful here.) 2) 25.22 From among the carbohydrates shown in Problem 25.20 choose the one(s) that (a) Belong to the 1 series (b) Are deoxy sugars (c) Are branched-chain sugars (d) Are ketoses (e) Are furanose forms (f) Have the a configuration at their anomeric carbon 25.23 How many pentuloses are possible? Write their Fischer projections. 25.24 The Fischer projection of the branched-chain carbohydrate D-apiose has been presented in Section 25.12. (a) How many stereogenic centers are in the open-chain form of D-apiose? (b) Does D-apiose form an optically active alditol on reduction? (c) How many stereogenic centers are in the furanose forms of D-apiose? (d) How many stercoisomeric furanose forms of D-apiose are possible? Write their Haworth formulas. 25.25 Treatment of D-mannose with methanol in the presence of an acid catalyst yields four iso- meric products having the molecular formula C,Hj40. What are these four products? 25.26 Maltose and cellobiose (Section 25.14) are examples of disaccharides derived from D- glucopyranosyl units. (a) How many other disaccharides are possible that meet this structural requirement? (b) How many of these are reducing sugars? Forward Main Menul Toe] Study Guide TOC Student OLC 1011 MHHE Website 1012 CHAPTER TWENTYFIVE Carbohydrates 25.27 Gentiobiose has the molecular formula C1>H>,0n and has been isolated from gentian root and by hydrolysis of amygdalin. Gentiobiose exists in two different forms, one melting at 86ºC and the other at 190C. The lower melting form is dextrorotatory (o]g” +16º), the higher melt- ing one is levorotatory (Lad —6º). The rotation of an aqueous solution of either form, however, gradually changes until a final value of [aJp +9.6º is observed. Hydrolysis of gentiobiose is effi- cientIy catalyzed by emulsin and produces two moles of D-glucose per mole of gentiobiose. Gen- tiobiose forms an octamethyl ether, which on hydrolysis in dilute acid yields 2,3,4,6-tetra-O- methyl-D-glucose and 2,3,4-tri-O-methyl-D-glucose. What is the structure of gentiobiose? 25.28 Cyanogenic glycosides are potentially toxic because they liberate hydrogen cyanide on enzyme-catalyzed or acidic hydrolysis. Give a mechanistic explanation for this behavior for the specific cases of CH,0H coH o Na po A ope Linamarin Laetrile 25.29 The following are the more stable anomers of the pyranose forms of D-glucose, D-mannose, and p-galactose: HOCH, o HOCH, O] PIA NDA HO B-D-Glucopyranose a-D-Mannopyranose B-D-Galactopyranose (64% at equilibrium) (689% at equilibrium) (64% at equilibrium) On the basis of these empirical observations and your own knowledge of steric effects in six- membered rings, predict the preferred form (a- or -pyranose) at equilibrium in aqueous solution for each of the following: (a) D-Gulose (c) D-Xylose (b) D-Talose (d) D-Lyxose 25.30 Basing your answers on the general mechanism for the first stage of acid-catalyzed acetal hydrolysis Hº, fast slow HO, fast Pago RaÇOR' = RaCOR' PagoR + Hº ) OCH; O, oH Tá “ct Acetal Hemiacetal suggest reasonable explanations for the following observations: (a) Methyl a-D-fructofuranoside (compound A) undergoes acid-catalyzed hydrolysis some 10º times faster than methyl a-D-glucofuranoside (compound B). E Forward Main Menul Toe] Study Guide TOC) Student OLC| MHHE Website Problems HOCH, O cmon NE HO/6cn, oH H H oH Compound A Compound B (b) The B-methyl glucopyranoside of 2-deoxy-D-glucose (compound C) undergoes hydrol- ysis several thousand times faster than that of D-glucose (compound D). HOCH, cH0H HO 9, HO 9, Ho OCH; Ho OCH; Ho Compound € Compound D 25.31 p-Altrosan is converted to D-altrose by dilute aqueous acid. Suggest a reasonable mecha- nism for this reaction. O H + HO > Daltrose oH OH HO D-Altrosan 25.32 When D-galactose was heated at 165ºC, a small amount of compound A was isolated: cHo H—oH o HOo——H oH de, no hoy Ho H—oH OH cHoH D-Galactose Compound A The structure of compound A was established, in part, by converting it to known compounds. Treat- ment of A with excess methyI iodide in the presence of silver oxide, followed by hydrolysis with dilute hydrochloric acid, gave a trimethyl ether of D-galactose. Comparing this trimethyl ether with known trimethyl ethers of D-galactose allowed the structure of compound A to be deduced. How many trimethyl ethers of D-galactose are there? Which one is the same as the product derived from compound À? 25.33 Phlorizin is obtained from the root bark of apple, pear, cherry, and plum trees. It has the molecular formula C»/H>401 and yields a compound A and D-glucose on hydrolysis in the pres- ence of emulsin. When phlorizin is treated with excess methyl iodide in the presence of potassium E Forward Main Menul Toe] Study Guide TOC Student OLC 1013 MHHE Website