CHAPTER TWENTY-FIVE Carbohydrat CH-OH CH=O Pyranose ring H volves this ChOH hydroxyl group Eclipsed OH HO OH OH OH OH 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 CH2OH 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 of the chair conformation of H OCHi B-D-glucopyranos Ho- H OH β D-Glucopyrano H H HOCH HO OH OH HH OH OH 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 o iso- mer;all the other substituents are equatorial Other aldohexoses behave similarly in adopting chair conformations that permit the CH2OH substituent to occupy an equatorial orientation. Normally the Ch2oh group is the bulkiest, most conformationally demanding substituent in the pyranose form of a hexose. Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
Like aldopentoses, aldohexoses such as D-glucose are capable of forming two furanose forms ( and ) and two pyranose forms ( and ). The Haworth representations of the pyranose forms of D-glucose are constructed as shown in Figure 25.4; each has a CH2OH 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 crystallographic studies of a large number of carbohydrates reveal that the six-membered pyranose ring of D-glucose adopts a chair conformation: All the ring substituents other than hydrogen in -D-glucopyranose are equatorial in the most stable chair conformation. Only the anomeric hydroxyl group is axial in the isomer; all the other substituents are equatorial. Other aldohexoses behave similarly in adopting chair conformations that permit the CH2OH substituent to occupy an equatorial orientation. Normally the CH2OH group is the bulkiest, most conformationally demanding substituent in the pyranose form of a hexose. O H H H HO H OH OH OH HOCH2 -D-Glucopyranose O H H H HO H OH OH OH HOCH2 -D-Glucopyranose H HOCH2 O OH HO OH HO H H H H OH HOCH2 O OH HO H HO H H H H O H H H HO H OH OH OH -D-Ribopyranose O H H H HO H OH OH OH -D-Ribopyranose Pyranose ring formation involves this hydroxyl group H CHO CH2OH OH H OH H OH D-Ribose CH2 OH H H H HO HO OH 4 CH O 5 3 2 1 Eclipsed conformation of D-ribose 982 CHAPTER TWENTY-FIVE Carbohydrates Make a molecular model of the chair conformation of -D-glucopyranose. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
5.7 Cyclic Forms of Carbohydrates: Pyranose Forms CHO H OH CHOH 2 H OH H-OH 0、H CHOH (hydroxyl group at Eclipsed conformation of D-Glucos C-5 is involved in pyranose hydroxyl at C-5 is not properly ing formation) oriented for ring formation rotate about C-4-C- bond in anticlockwise direction 2 HOCH HOCH H OH O H H HO\OH HO \OH HO、OH OH B-D-Glucopyranose a-D-Glucopyranose Ecl proper orientation for pyranose FIGURE 25.4 Haworth for- PROBLEM 25.6 Clearly represent the most stable conformation of the B-pyra- mulas for a- and B-pyranose nose form of each of the following sugars (a) D-Galactose (c) L-Mannose (b)D-Mannose (d) L-Ribose SAMPLE SOLUTION (a)By analogy with the procedure outlined for D-glucose in Figure 25. 4, first generate a Haworth formula for B-D-galactopyranose CHO CH2OH HO H OH OH OH CH2OH D-Galactose B-D-GalactopyraI (Haworth form Next, redraw the planar Haworth formula more realistically as a chair conforma tion, choosing the one that has the Ch2 Oh group equatorial Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
PROBLEM 25.6 Clearly represent the most stable conformation of the -pyranose form of each of the following sugars: (a) D-Galactose (c) L-Mannose (b) D-Mannose (d) L-Ribose SAMPLE SOLUTION (a) By analogy with the procedure outlined for D-glucose in Figure 25.4, first generate a Haworth formula for -D-galactopyranose: Next, redraw the planar Haworth formula more realistically as a chair conformation, choosing the one that has the CH2OH group equatorial. H CHO CH2OH OH H OH HO H HO H D-Galactose CH2OH H OH H OH H OH CH O HO H O H OH H OH HOCH2 HO H OH H -D-Galactopyranose (Haworth formula) 25.7 Cyclic Forms of Carbohydrates: Pyranose Forms 983 CHO OH OH CH2OH H OH H HO H H 1 2 3 4 5 6 1 3 2 4 5 6 HO H H OH OH H OH H CH2OH C O H D-Glucose (hydroxyl group at C-5 is involved in pyranose ring formation) Eclipsed conformation of D-Glucose; hydroxyl at C-5 is not properly oriented for ring formation HOCH2 HO H OH H OH H H OH O -D-Glucopyranose H HOCH2 HO H OH H OH H H OH O -D-Glucopyranose H 1 3 2 4 5 6 HO H OH H OH H C O H HOCH2 O H rotate about C-4–C-5 bond in anticlockwise direction Eclipsed conformation of D-glucose in proper orientation for pyranose ring formation H FIGURE 25.4 Haworth formulas for - and -pyranose forms of D-glucose. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
CHAPTER TWENTY-FIVE Carbohydrat HOCH HOCH2 O rather than HO H H Most stable chair Less stable chair. Galactose differs from glucose in configuration at C-4. The C-4 hydroxyl is axial in B-D-galactopyranose, but it is equatorial in B-D-glucopyranos Since six-membered rings are normally less strained than five-membered pyranose forms are usually present in greater amounts than furanose forms at equilib- rium, and the concentration of the open-chain form is quite small. The distribution of carbohydrates among their various hemiacetal forms has been examined by using H and C NMR spectroscopy. In aqueous solution, for example, D-ribose is found to contain the various a and B-furanose and pyranose forms in the amounts shown in Figure 25.5 The concentration of the open-chain form at equilibrium is too small to measure directly Nevertheless, it occupies a central position, in that interconversions of a and B anomers and furanose and pyranose forms take place by way of the open-chain form as an inter mediate. As will be seen later, certain chemical reactions also proceed by way of the open-chain form H H HOCH HO H OH OHOH B-D-Ribopyranose(56%0) B-D-Ribofuranose(18%) H CH,OH H of d-ribose HOCH FIGURE 25 ution of OH furans HO H OH OH ae-D-Ribopyranose(20%) a-D-Ribofuranose(6%) spectroscopy Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
Galactose differs from glucose in configuration at C-4. The C-4 hydroxyl is axial in -D-galactopyranose, but it is equatorial in -D-glucopyranose. Since six-membered rings are normally less strained than five-membered ones, pyranose forms are usually present in greater amounts than furanose forms at equilibrium, and the concentration of the open-chain form is quite small. The distribution of carbohydrates among their various hemiacetal forms has been examined by using 1 H and 13C NMR spectroscopy. In aqueous solution, for example, D-ribose is found to contain the various and -furanose and pyranose forms in the amounts shown in Figure 25.5. The concentration of the open-chain form at equilibrium is too small to measure directly. Nevertheless, it occupies a central position, in that interconversions of and anomers and furanose and pyranose forms take place by way of the open-chain form as an intermediate. As will be seen later, certain chemical reactions also proceed by way of the open-chain form. 984 CHAPTER TWENTY-FIVE Carbohydrates O H OH H OH HOCH2 HO H OH H Most stable chair conformation of -D-galactopyranose rather than Less stable chair; CH2OH group is axial H HOCH2 O OH HO OH H H H HO H H H HOCH2 O OH HO H H OH H OH -D-Ribopyranose (56%) C OH CH2OH H OH H O O OH OH OH H H H H H OH H H OH HO H HO H H -D-Ribofuranose (18%) H OH H O Open-chain form of D-ribose (less than 1%) -D-Ribopyranose (20%) -D-Ribofuranose (6%) O OH OH OH H H H H H H O OH H H HO H HO H OH HOCH2 HOCH2 FIGURE 25.5 Distribution of furanose, pyranose, and open-chain forms of D-ribose in aqueous solution as measured by 1 H and 13C NMR spectroscopy. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
25. 8 Mutarotation 25.8 MUTAROTATION In spite of their easy interconversion in solution, a and B forms of carbohydrates are capable of independent existence, and many have been isolated in pure form as crys talline solids. When crystallized from ethanol, D-glucose yields ax-D-glucopyranose, mp 146C, [a]p +112. 2. Crystallization from a water-ethanol mixture produces B-D- glucopyranose, mp 148-155C, [aD +18.7. In the solid state the two forms do not terconvert and are stable indefinitely. Their structures have been unambiguously con- firmed by X-ray crystallography The optical rotations just cited for each isomer are those measured immediately after each one is dissolved in water. On standing the rotation of the solution containing the a isomer decreases from +112.20 to +5250. the rotation of the solution of the B isomer increases from +18.7 to the same value of +52.50. This phenomenon is called mutarotation. What is happening is that each solution, initially containing only one homeric form, undergoes equilibration to the same mixture of a-and p-pyranose forms The open-chain form is an intermediate in the process. HOCH- HOCHe oh HOCH HO 、HOO CH=O HO OH H a-D-Glucopyranose D-Glucopyranose f D-gluco (mp148-155C: l+112.29 The distribution between the a and B anomeric forms at equilibrium is readily cal- culated from the optical rotations of the pure isomers and the final optical rotation of the glucose in w'y of D- established that only the pyranose forms of D-glucose are present in significant quanti- Ge she cies the r detected solution, and is determined to be 36% a to 64%B. Independent measurements have fiv furanose(.14%), and and the hydrate of the open PROBLEM 25.7 The specific optical rotations of pure a-and B-D-mannopyranose chain form(0.0045%) are +29.3 and.0, respectively. When either form is dissolved in water mutarotation occurs, and the observed rotation of the solution changes until a final rotation of +14.20 is observed. Assuming that only a- and B-pyranose forms are present, calculate the percent of each isomer at equilibrium It's not possible to tell by inspection whether the a-or B-pyranose form of a particular carbohydrate predominates at equilibrium. As just described, the B-pyranose form is the major species present in an aqueous solution of D-glucose, whereas the a-pyranose form predominates in a solution of D-mannose(Problem 25.7). The relative abundance of a-and B-pyranose forms in solution is a complicated issue and depends on several factors. One is solvation of the anomeric hydroxyl group. An equatorial OH is less crowded and better solvated by water than an axial one. This effect stabilizes the The anomeric effect is best B-pyranose form in aqueous solution. A second factor, called the anomeric effect, plained by a molecular or involves an electronic interaction between the ring oxygen and the anomeric substituent bital analysis that is beyond and preferentially stabilizes the axial OH of the a-pyranose form. Because the two effects the scope of this text. Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
25.8 MUTAROTATION In spite of their easy interconversion in solution, and forms of carbohydrates are capable of independent existence, and many have been isolated in pure form as crystalline solids. When crystallized from ethanol, D-glucose yields -D-glucopyranose, mp 146°C, []D 112.2°. Crystallization from a water–ethanol mixture produces -Dglucopyranose, mp 148–155°C, []D 18.7°. In the solid state the two forms do not interconvert and are stable indefinitely. Their structures have been unambiguously con- firmed by X-ray crystallography. The optical rotations just cited for each isomer are those measured immediately after each one is dissolved in water. On standing, the rotation of the solution containing the isomer decreases from 112.2° to 52.5°; the rotation of the solution of the isomer increases from 18.7° to the same value of 52.5°. This phenomenon is called mutarotation. What is happening is that each solution, initially containing only one anomeric form, undergoes equilibration to the same mixture of - and -pyranose forms. The open-chain form is an intermediate in the process. The distribution between the and anomeric forms at equilibrium is readily calculated from the optical rotations of the pure isomers and the final optical rotation of the solution, and is determined to be 36% to 64% . Independent measurements have established that only the pyranose forms of D-glucose are present in significant quantities at equilibrium. PROBLEM 25.7 The specific optical rotations of pure - and -D-mannopyranose are 29.3° and 17.0°, respectively. When either form is dissolved in water, mutarotation occurs, and the observed rotation of the solution changes until a final rotation of 14.2° is observed. Assuming that only - and -pyranose forms are present, calculate the percent of each isomer at equilibrium. It’s not possible to tell by inspection whether the - or -pyranose form of a particular carbohydrate predominates at equilibrium. As just described, the -pyranose form is the major species present in an aqueous solution of D-glucose, whereas the -pyranose form predominates in a solution of D-mannose (Problem 25.7). The relative abundance of -and -pyranose forms in solution is a complicated issue and depends on several factors. One is solvation of the anomeric hydroxyl group. An equatorial OH is less crowded and better solvated by water than an axial one. This effect stabilizes the -pyranose form in aqueous solution. A second factor, called the anomeric effect, involves an electronic interaction between the ring oxygen and the anomeric substituent and preferentially stabilizes the axial OH of the -pyranose form. Because the two effects 25.8 Mutarotation 985 -D-Glucopyranose (mp 146°C; []D 112.2°) Open-chain form of D-glucose CHœO -D-Glucopyranose (mp 148–155°C; []D 18.7°) OH HOCH2 O OH HO HO HOCH2 OH OH HO HO OH HOCH2 O OH HO HO A 13C NMR study of Dglucose in water detected five species: the -pyranose (38.8%), -pyranose (60.9%), -furanose (0.14%), and -furanose (0.15%) forms, and the hydrate of the openchain form (0.0045%). The anomeric effect is best explained by a molecular orbital analysis that is beyond the scope of this text. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
CHAPTER TWENTY-FIVE Carbohydrat operate in different directions but are comparable in magnitude in aqueous solution, the a-pyranose form is more abundant for some carbohydrates and the p-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-fructos CH,OH CH,OH CH,OH CH,OH CH,O CH,OH D-Ribulose L-Xylulose D-Fructose (a 2-ketopentose (a 2-ketopentose(a 2-ketohexose also that is a key excreted ssive known as levulose amounts in the urine it is found in honey photosynthesis) of persons afflicted and is signficantly with the mild genetic sweeter than table disorder pentosuria) In 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 PROBLEM 25.8 How many ketotetroses are possible? Write Fischer projections 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 H CH,OH H,OH H,OH H Ho OH Ho OH Eclipsed conformation of B-D-Ribulofuranose c-D-Ribulofuranose D-ribulose Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
operate in different directions but are comparable in magnitude in aqueous solution, the -pyranose form is more abundant for some carbohydrates and the -pyranose form for others. 25.9 KETOSES Up to this point all our attention has been directed toward aldoses, carbohydrates having 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. Nevertheless, a large number of ketoses are known, and several of them are pivotal intermediates in carbohydrate biosynthesis and metabolism. Examples of some ketoses include D-ribulose, L-xylulose, and D-fructose: In these three examples the carbonyl group is located at C-2, which is the most common location for the carbonyl function in naturally occurring ketoses. PROBLEM 25.8 How many ketotetroses are possible? Write Fischer projections 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. O H H H H H HO OH C CH2OH O Eclipsed conformation of D-ribulose O H H HO OH CH2OH OH -D-Ribulofuranose O H H HO OH OH CH2OH -D-Ribulofuranose D-Ribulose (a 2-ketopentose that is a key compound in photosynthesis) CH2OH CH2OH H OH H OH C O D-Fructose (a 2-ketohexose also known as levulose; it is found in honey and is signficantly sweeter than table sugar) CH2OH CH2OH HO H H OH H OH C O L-Xylulose (a 2-ketopentose excreted in excessive amounts in the urine of persons afflicted with the mild genetic disorder pentosuria) CH2OH CH2OH H OH HO H C O 986 CHAPTER TWENTY-FIVE Carbohydrates Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website