Carbohydrates

2. Carbohydrates Carbohydrate • Broad class of polyhydroxylated aldehydes and ketones commonly called sugars • Synthesized by green plants during photosynthesis • Name derived from glucose • Glucose was the first simple carbohydrate obtained in pure form • Molecular formula of glucose, C6H12O6, was thought to be a “hydrate of carbon, C6(H2O)6” • ~ 50% of the dry weight of earth’s biomass consists of glucose polymers

3. Carbohydrates Carbohydrates act as chemical intermediates by which solar energy is stored and used to support life on earth

4. 21.1 Classification of Carbohydrates Carbohydrates are classed as simple or complex • Simple sugars , or monosaccharides • Carbohydrates like glucose and fructose that cannot be converted into more simple sugars by hydrolysis • Complex carbohydrates • Made up of two or more simple sugars • Sucrose is a disaccharide comprised of one glucose and one fructose • Cellulose is a polysaccharide comprised of several thousand linked glucose units

5. Classification of Carbohydrates Monosaccharides are classified as aldoses or ketoses • -ose suffix designates a carbohydrate • aldo- prefix identifies an aldehyde carbonyl group in the sugar • keto- prefix identifies a ketone carbonyl group in the sugar • Number of carbons indicated by the numerical prefix tri-, tetra-, pent-, hex-

6. 21.2 Depicting Carbohydrate Stereochemistry: Fischer Projections Fischer projections • Suggested by Emil Fischer (1891) • Method to project a tetrahedral carbon onto a flat surface • Tetrahedral carbon represented by two crossed lines • Horizontal lines come out of the page • Vertical lines go back into page

7. Depicting Carbohydrate Stereochemistry: Fischer Projections A Fischer projection of (R)-glyderaldehyde

8. Depicting Carbohydrate Stereochemistry: Fischer Projections Rules for manipulating Fischer projections: • A Fischer projection can be rotated on the page by 180°, but not by 90° or 270° • Only a 180° rotation maintains the Fischer convention by keeping the same substituent groups going into and coming out of the plane

9. Depicting Carbohydrate Stereochemistry: Fischer Projections • A 90° rotation breaks the Fischer convention by exchanging the groups that go into and come out of the plane • A 90° or a 270° rotation changes the representation to the enantiomer

10. Depicting Carbohydrate Stereochemistry: Fischer Projections • A Fischer projection can have one group held steady while the other three rotate in either a clockwise or a counterclockwise direction • Effect is to simply rotate around a single bond

11. Depicting Carbohydrate Stereochemistry: Fischer Projections Three steps for assigning R,S stereochemical designations in Fischer projections • Assign priorities to the four substituents in the usual way • Place the group of lowest priority, usually H, at the top of the Fischer projection by using one of the allowed motions • The lowest-priority group is thus oriented back away from viewer • Determine the direction of rotation 1→2→3 of the remaining three groups and assign R or S configuration

12. Depicting Carbohydrate Stereochemistry: Fischer Projections Carbohydrates with more than one chirality center are shown in Fischer projection by stacking the centers on top of one another • By convention the carbonyl carbon is always placed at or near the top

13. Worked Example 21.1Assigning R or S Configuration to a Fischer Projection Assign R or S configuration to the following Fischer projection of alanine:

14. Worked Example 21.1Assigning R or S Configuration to a Fischer Projection Strategy • Follow the steps listed in the text • Assign priorities to the four substituents on the chiral carbon • Manipulate the Fischer projection to place the group of lowest priority at the top by carrying out one of the allowed motions • Determine the direction 1→2→3 of the remaining three groups

15. Worked Example 21.1Assigning R or S Configuration to a Fischer Projection Solution • The priorities of the groups are (1) –NH2, (2) –CO2H, (3) –CH3, and (4) –H • To bring the lowest priority (–H ) to the top we might want to hold the –CH3 group steady while rotating the other three groups counterclockwise

16. Worked Example 21.1Assigning R or S Configuration to a Fischer Projection • Going from first- to second- to third-highest priority requires a counterclockwise turn, corresponding to S stereochemistry

17. 21.3 D,L Sugars Glyceraldehyde • Simplest aldose • One chirality center • Two enantiomeric (mirror-image) forms • Only dextrorotatory enantiomer (–)-glyceraldehyde occurs naturally • (+)-Glyceraldehyde has the R configuration • (R)-(+)-glyceraldehyde is also referred to as D-glyderaldehyde (D for dextrorotatory) • (S)-(–)-glyceraldehyde in also known as L-glyceraldehyde (L for levorotatory)

18. D,L Sugars Virtually all naturally occurring monosaccharides have the same R stereochemical configuration as D-glyceraldehyde at the chirality center farthest from the carbonyl group • In Fischer projections most naturally occurring sugars have the hydroxyl group at the bottom chirality center pointing to the right • Such compounds known as D sugars

19. D,L Sugars L sugars have an S stereochemical configuration at the chirality center farthest from the carbonyl group • –OH group pointing to the left in Fischer projections • An L sugar is the mirror image (enantiomer) of the corresponding D sugar D and L sugars can be either dextrorotatory or levorotatory • D and L designations only specify the stereochemical configuration at the one chirality center farthest away from the carbonyl group

20. 21.4 Configurations of the Aldoses Aldotetroses are four-carbon sugars with two chirality centers and an aldehyde carbonyl group • 22 = 4 possible stereoisomeric aldotetroses • Two D,L pairs or enantiomers named erythrose and threose Aldopentoses are five-carbon sugars with three chirality centers and an aldehyde carbonyl group • 23 = 8 possible stereoisomeric aldopentoses • Four D,L pairs of enantiomers named ribose, arabinose, xylose, and lyxose • All but lyxose occur widely • D-Ribose is an important constituent in RNA • L-Arabinose is found in plants • D-Xylose is found in both plants and animals

21. Configurations of the Aldoses Aldohexoses are six-carbon sugars with four chirality centers and an aldehyde carbonyl group • 24 = 16 possible stereoisomeric aldohexoses • Eight D,L pairs of enantiomers named allose, altrose, glucose, mannose, gulose, idose, galactose, and talose • D-Glucose from starch and cellulose and D-galactose from gums and fruit pectins occur widely in nature

22. Configurations of the Aldoses Configurations of D-aldoses • -OH groups on right side (R) or left side (L) of the chain

23. Configurations of the Aldoses Remembering the names and structures of the eight D aldohexoses: • Set up eight Fischer projections with the –CHO group on top and the –CH2OH group at the bottom • At C5, place all eight –OH groups to the right (D series) • At C4, alternate four –OH groups to the right, four to the left • At C3, alternate two –OH groups to the right, two to the left • At C2, alternate –OH groups right, left, right, left • Name the eight isomers using the mnemonic “All altruists gladly make gum in gallon tanks.” (Structures of the four D aldopentoses: “Ribs are extra lean.”

24. Worked Example 21.2Drawing a Fischer Projection Draw a Fischer projection of L-fructose.

25. Worked Example 21.2Drawing a Fischer Projection Strategy • Since L-fructose is the enantiomer of D-fructose, look at the structure of D-fructose and reverse the configuration at each chirality center.

26. Worked Example 21.2Drawing a Fischer Projection Solution

27. 21.5 Cyclic Structures of Monosaccharides: Anomers Aldehydes and ketones undergo a rapid and reversible nucleophilic addition reaction with alcohols to form hemiacetals Monosaccharides undergo intramolecular nucleophilic additions • The carbonyl and hydroxyl groups of the same molecule react to form cyclic hemiacetals

28. Cyclic Structures of Monosaccharides: Anomers Glucose exists in aqueous solution primarily in the six-membered, pyranose ring form • Results from intramolecular nucleophilic addition of the –OH group at C5 to the C1 carbonyl group • The name pyranose is derived from pyran • Pyran is the name of the unsaturated six-membered cyclic ether • Pyranose rings have chairlike geometry with axial and equatorial substituents

29. Cyclic Structures of Monosaccharides: Anomers • Pyranose rings are drawn placing the hemiacetal oxygen at the right rear • –OH group of hemiacetal can either be on the top or bottom face of the ring • Terminal –CH2OH group is on the top face of the ring in D sugars and on the bottom face of the ring in L sugars • When an open-chain monosaccharide cyclizes to a pyranose ring form a new chirality center is generated at the former carbonyl carbon • The two diastereomers are called anomers and the hemiacetal carbon atom is referred to as the anomeric center

30. Cyclic Structures of Monosaccharides: Anomers Two anomers formed by cyclization of glucose • The molecule whose newly formed –OH group at C1 is cis to the oxygen atom on the lowest chirality center (C5) in a Fischer projection is the a anomer • The molecule whose newly formed –OH group at C1 is trans to the oxygen atom on the lowest chirality center (C5) in a Fischer projection is the b anomer

31. Cyclic Structures of Monosaccharides: Anomers Some monosaccharides also exist in a five-membered cyclic hemiacetal form called a furanose • D-Fructose exists in both the pyranose and the furanose forms • The two pyranose anomers result from addition of C6 –OH group to the C2 carbonyl • The two furanose anomers result from addition of C5 –OH group to the C2 carbonyl

32. Cyclic Structures of Monosaccharides: Anomers Both anomers of D-glucopyranose can be crystallized and purified • Pure a-D-glucopyranose • Melting point = 146 °C • [a]D specific rotation = +112.2 • Pureb-D-glucopyranose • Melting point = 148-155 °C • [b]D specific rotation = +18.7

33. Cyclic Structures of Monosaccharides: Anomers • When a sample of either pure anomer of D-glucopyranose is dissolved in water its optical rotation slowly changes and reaches a constant value of +52.6 • The specific rotation of a-D-glucopyranose decreases from +112.2 to +52.6 when dissolved in aqueous solution • The specific rotation of b-D-glucopyranose increases from +18.7 to +52.6 when dissolved in aqueous solution • This change in optical rotation is due to the slow conversion of the pure anomers into a 37 : 63 equilibrium mixture and is known as mutarotation

34. Cyclic Structures of Monosaccharides: Anomers Mutarotation of D-glucopyranose • Mutarotation occurs by a reversible ring opening of each anomer to the open-chain aldehyde followed by reclosure • Mutarotation is catalyzed by both acid and base

35. Worked Example 21.3Drawing the Chair Conformation of an Aldohexose D-Mannose differs from D-glucose in it stereochemistry at C2. Draw D-mannose in its chairlike pyranose form.

36. Worked Example 21.3Drawing the Chair Conformation of an Aldohexose Strategy • First draw a Fischer projection of D-mannose • Lay it on its side and curl it around so that the –CHO group (C1) is toward the right front and the –CH2OH group (C6) is toward the left rear • Connect the –OH at C5 to the C1 carbonyl group to form the pyranose ring • In drawing the chair form raise the leftmost carbon (C4) up and drop the rightmost carbon (C1) down

37. Worked Example 21.3Drawing the Chair Conformation of an Aldohexose Solution

38. Worked Example 21.4Drawing the Chair Conformation of an Aldohexose Draw b-L-glucopyranose in its more stable chair conformation

39. Worked Example 21.4Drawing the Chair Conformation of an Aldohexose Strategy • It’s probably easiest to begin by drawing the chair conformation of b-D-glucopyranose • Then draw its mirror-image L enantiomer by changing the stereochemistry at every position on the ring • Carry out a ring-flip to give the more stable chair conformation • Note that the –CH2OH group is on the bottom face of the ring in the L enantiomer

40. Worked Example 21.4Drawing the Chair Conformation of an Aldohexose Solution

41. 21.6 Reactions of Monosaccharides Ester and Ether Formation • Monosaccharides exhibit chemistry similar to simple alcohols • Usually soluble in water but insoluble in organic solvents • Do not easily form crystals upon removal of water • Can be converted into esters and ethers • Ester and ether derivatives are soluble in organic solvents and are easily purified and crystallized

42. Reactions of Monosaccharides • Esterification is normally carried out by treating the carbohydrate with an acid chloride or acid anhydride in presence of base • All –OH groups react including the anomeric –OH group

43. Reactions of Monosaccharides Carbohydrates are converted into ethers by treatment with an alkyl halide in the presence of base – the Williamson ether synthesis • Silver oxide (Ag2O) gives high yields of ethers without degrading the sensitive carbohydrate molecules

44. Reactions of Monosaccharides Glycoside Formation • Hemiacetals yield acetals upon treatment with an alcohol and an acid catalyst • Treatment of monosaccharide hemiacetals with an alcohol and acid catalyst yields an acetal, called a glycoside

45. Reactions of Monosaccharides • Glycosides are named by first citing the alkyl group and then replacing the –ose ending of the sugar with –oside • Glycosides are stable in neutral water and do not mutarotate • Glycosides hydrolyze back to free monosaccharide plus alcohol upon treatment with aqueous acid • Glycosides are abundant in nature • Digitoxigenin – used for treatment of heart disease

46. Reactions of Monosaccharides Biological Ester Formation: Phosphorylation Glycoconjugates • Carbohydrates linked through their anomeric center to other biological molecules such as lipids (glycolipids) or proteins (glycoproteins) • Constitute components of cell walls and participate in cell-type recognition and identification

47. Reactions of Monosaccharides • Glucoconjugate formation occurs by reaction of the lipid or protein with a glycosyl nucleoside diphosphate • Glycosyl nucleoside diphosphate is initially formed by phosphorylation of monosaccharide with ATP to give glycosyl phosphate

48. Reactions of Monosaccharides • Reaction with UTP forms a glycosyl uridine 5′-diphosphate • Nucleophilic substitution by an –OH (or –NH2) group on a protein then gives the glycoprotein

49. Reactions of Monosaccharides Reduction of Monosaccharides • Treatment of an aldose or ketose with NaBH4 reduces it to a polyalcohol called an alditol • Reduction occurs by reaction of the open-chain form present in aldehyde/ketone hemiacetal equilibrium • D-Glucitol, also known as D-sorbitol, is present in many fruits and berries and is used as a sweetener and sugar substitute

50. Reactions of Monosaccharides Oxidation of Monosaccharides • Aldoses are easily oxidized to yield corresponding carboxylic acids called aldonic acids • Oxidizing agents include: • Tollen’s reagent (Ag+ in aqueous NH3) • Gives shiny metallic silver mirror on walls of reaction tube or flask • Fehling’s reagent (Cu2+ in aqueous sodium tartrate) • Gives reddish precipitate of Cu2O • Benedict’s reagent (Cu2+ in aqueous sodium citrate) • Gives reddish precipitate of Cu2O (All three reactions serve as simple chemical tests for reducing sugars)