Foxglove (Digitalis purpurea),an ornamental flowering plant.is the source of digitoxin anddigitalis, medicines used in cardiol-ogy to reduce pulse rate, regularizeheart rhythm, and strengthen heartbeat. Inset: digitoxose, a monosac-charide obtained on hydrolysis ofdigitoxin. See Problem 25.15.

OUTLINE

CarbohydrateA polyhydroxyaldehyde, a polyhy-droxyketone, or a substance thatgives these compounds on hydrolysis.

25.125.2

25.3

25.4

25.525.6

MonosaccharidesThe Cyclic Structure ofMonosaccharidesReactions ofMonosaccharidesDisaccharides andOligosaccharidesPolysaccharidesGlucosaminoglycans

Online homework for thischapter may be assignedin Organic OWL.

Carbohydrates are the most abundant organic compounds in the plant world.They act as storehouses of chemical energy (glucose, starch, glycogen); arecomponents of supportive structures in plants (cellulose), crustacean shells(chitin), and connective tissues in animals (glucosaminoglycans); and are essentialcomponents of nucleic acids (n-ribose and 2-deoxy-n-ribose). Carbohydrates makeup about three fourths of the dry weight of plants. Animals (including humans) gettheir carbohydrates by eating plants, but they do not store much of what they con-sume. Less than 1%of the body weight of animals is made up of carbohydrates.

The name carbohydrate means hydrate of carbon and derives from the formulaCn(H20)m' Following are two examples of carbohydrates with molecular formulasthat can be written alternatively as hydrates of carbon.

Gluc ose (blood sugar): C6H 120 6, or alternatively C6(H20)6Sucrose (table sugar): C12H220n, or alternatively C12(H20)n

Not all carbohydrates, however, have this general formula. Some contain too fewoxygen atoms to fit this formula, and some others contain too many oxygens. Somealso contain nitrogen. The term carbohydrate has become so firmly rooted in chem-ical nomenclature that, although not completely accurate, it persists as the name forthis class of compounds.

At the molecular level, most carbohydrates are polyhydroxyaldehydes, poly-hydroxyketones, or compounds that yield either of these after hydrolysis. Therefore,the chemistry of carbohydrates is essentially the chemistry of hydroxyl groups and car-bonyl groups, and of the acetal bonds formed between these two functional groups.

The fact that carbohydrates have only two types of functional groups, however,belies the complexity of their chemistry. All but the simplest carbohydrates containmultiple chiral centers. For example, glucose, the most abundant carbohydrate inthe biological world, contains one aldehyde group, one primary and four second-ary hydroxyl groups, and four chiral centers. Working with molecules of this com-plexity presents enormous challenges to organic chemists and biochemists alike.

976

25.1 MonosaccharidesA. Structure and Nomenclature

Monosaccharides Classifiedby Number of Carbon Atoms

There are only two trioses: the aldotriose glyceraldehyde and the ketotriosedihydroxyacetone.

Name Formula

Triose CSH60 STetrose C4Hs0 4Pentose C5H lOO5Hexose C6H120 6Heptose C7H140 7Octose CSH160 S

1,3-Dihydroxypropanone, morecommonly known as dihydroxy-acetone, is the active ingredient inartificial tanning agents such asMan-Tan and Magic Tan.

MonosaccharideA carbohydrate that cannot be hy-drolyzed to a simpler carbohydrate.

AldoseA monosaccharide containing analdehyde group.

KetoseA monosaccharide containing aketone group.

1H20HC=OI

CH20H

Dihydroxyacetone(a ketotriose)

CHOI

CHOHI

CH20H

Glyceraldehyde(an aldotriose)

Monosaccharides have the general formula CnH 2nO" with one of the carbonsbeing the carbonyl group of either an aldehyde or a ketone. The most commonmonosaccharides have three to eight carbon atoms. The suffix -ose indicates thata molecule is a carbohydrate, and the prefixes tn., tetro, pent-, and so forth indicatethe number of carbon atoms in the chain. Monosaccharides containing an alde-hyde group are classified as aldoses; those containing a ketone group are classi-fied as ketoses.

Often the designations alda- and keta- are omitted, and these molecules arereferred to simply as trioses, tetroses, and the like.

Glyceraldehyde is a common name; the IUPAC name for this monosaccha-ride is 2,3-dihydroxypropanal. Similarly, dihydroxyacetone is a common name; itsIUPAC name is 1,3-dihydroxypropanone. The common names for these and othermonosaccharides, however, are so firmly rooted in the literature of organic chem-istry and biochemistry that they are used almost exclusively to refer to these com-pounds. Therefore, throughout our discussions of the chemistry and biochemistryof carbohydrates, we use the names most common in the literature of chemistryand biochemistry.

B. Fischer Projection FormulasGlyceraldehyde contains a chiral center and therefore exists as a pair of enantiomers.

(R)-Glyceraldehyde

~HO

(S)-Glyceraldehyde

25.1 Monosaccharides 977

ChemicalConnections

L-Ascorbic Acid (Vitamin C)

The structure of L-ascorbic acid (vitamin C) resemblesthat of a monosaccharide. In fact, this vitamin is synthe-sized both biochemically by plants and some animals andcommercially from D-glucose. Humans do not have theenzymes required for this synthesis and, therefore, wemust obtain it in the food we eat or as a vitamin supple-ment. Approximately 66 million kilograms of vitamin Care synthesized every year in the United States.

L-Ascorbic acid is very easily oxidized to L-dehydro-ascorbic acid, a diketone. Both L-ascorbic acid and

L-dehydroascorbic acid are physiologically active andare found together in most body fluids.

Ascorbic acid is one of the most important anti-oxidants (the H in the enolic OH is weakly bondedand easily abstracted by radicals). One of the mostimportant roles it plays may be to replenish the lipid-soluble antioxidant a-tocopherol by transferring ahydrogen atom to the tocopherol radical, formedby reaction with radicals in the autoxidation process(see Section 8.7).

Hf-clio~ OH 0L-Ascorbic acid

(Vitamin C)

oxidation'reduction

L-Dehydroascorbicacid

Units of n-ribose and 2-deoxy-n-ribose in nucleic acids and most other biologicalmolecules are found almost exclusively in the ,B-configuration.

Other monosaccharides also form five-membered cyclic hemiacetals. Followingare the five-membered cyclic hemiacetals of fructose.

a-D-Fructofuranose

lCH20H2 1C=O

H~*4~HH S OH

6CH20H

D-Fructose

'"

anomericca:bonJHOCH2 OH ({3)s~H~2H~lCH20H

HO HjJ-D-Fructofuranose

The ,B-n-fructofuranose form is found in the disaccharide sucrose (Section 25.4A).

B. Conformation RepresentationsA five-membered ring is so close to being planar that Haworth projections are ade-quate representations of furanoses. For pyranoses, however, the six-membered ringis more accurately represented as a chair conformation. Following are structural for-mulas for a-D-glucopyranose and ,B-n-glucopyranose drawn as chair conformations.

25.2 The Cyclic Structure of Monosaccharides 983

Figure 25.3 0 NJ 0 :5=N 0Structural formulas of the five 0:6 HN:YCH' J=Nmost important pyrimidine O~N I O~N I IN I N> HN I >and purine bases found in H2NA N NDNA and RNA. The hydrogenatom shown in grey is lost in I I Iforming an N-glycoside.

Uracil Cytosine Thymine Adenine Guanine

Just as the anomeric carbon of a cyclic hemiacetal undergoes reactionwith the -OH group of an alcohol to form a glycoside, it also undergoesreaction with the N-H group of an amine to form an N-glycoside. Especiallyimportant in the biological world are the N-glycosides formed between n-ribose and 2-deoxy-n-ribose, each as a furanose, and the heterocyclic aromat-ic amines uracil, cytosine, thymine, adenine, and guanine (Figure 25.3). N-Glycosides of these pyrimidine and purine bases are structural units of nucleicacids (Chapter 28).

Example 25.5Draw a structural formula for cytidine, the ,B-Nglycoside formed between D-ribofuranoseand cytosine.

Solution

NA~,,) I3-N-glycosidic bondo N/ /HO~C20 ~

H H ~H H anomeric carbon

HO OH

Cytidine

Problem 25.5Draw a structural formula for the ,B-Nglycoside formed between 2-deoxy-D-ribofuranoseand adenine.

B. Reduction to Alditols

AlditolThe product formed when theC=O group of a monosaccharideis reduced to a CHOH group.

986 Chapter 25 Carbohydrates

The carbonyl group of a monosaccharide can be reduced to a hydroxyl groupby a variety of reducing agents, including sodium borohydride and hydrogen inthe presence of a transition metal catalyst. The reduction products are knownas alditols. Reduction of n-glucose gives n-glucitol, more commonly knownas n-sorbitol. Note that n-glucose is shown here in the open-chain form. Onlya small amount of this form is present in solution, but, as it is reduced, theequilibrium between cyclic hemiacetal forms and the open-chain form shifts toreplace it.

CHO CH20H

H OH H OHCH20H HO H HO HHO~ ~ NaBH4 )

HO OH H OH H OHOH

H OH H OH

CH20H CH20H

f:l-D-Glucopyranose D-Glucose D-Glucitol(D-Sorbitol)

Sorbitol is found in the plant world in many berries and in cherries, plums,pears, apples, seaweed, and algae. It is about 60% as sweet as sucrose (tablesugar) and is used in the manufacture of candies and as a sugar substitute fordiabetics. D-Sorbitol is an important food additive, usually added to preventdehydration of foods and other materials on exposure to air because it bindswater strongly.

Other alditols common in the biological world are erythritol, D-mannitol, andxylitol. Xylitol is used as a sweetening agent in "sugarless" gum, candy, and sweetcereals.

CH20H

HO H

Ht ::Hi:: HO HH OH HO HH OH H OH H OH Many "sugar-free" productsCH20H CH20H CH20H contain sugar alcohols, such as~sorbitol and xylitol.

Erythritol D-Mannitol Xylitol

c. Oxidation to Aldonic Acids: Reducing SugarsAs we saw in Section 16.10A, aldehydes (RCHO) are oxidized to carboxylicacids (RCOOH) by several oxidizing agents, including oxygen, O2, Similarly,the aldehyde group of an aldose can be oxidized, under basic conditions,to a carboxylate group. Oxidizing agents for this purpose include brominein aqueous calcium carbonate (Br2' CaC03, H 20) and Tollens' solution[Ag(NH3h+]. Under these conditions, the cyclic form of an aldose is in equi-librium with the open-chain form, which is then oxidized by the mild oxidiz-ing agent. n-Glucose, for example, is oxidized to n-gluconate (the anion ofn-gluconic acid).

H~/H OH

CH20H HO HHO~ ~~HO OH H OH

OHH OH

CH20H

25.3 Reactions of Monosaccharides 987

Glucose oxidase is specific for 13-n-glucose. There-fore, complete oxidation of any sample containing bothl3-n-glucose and a-n-glucose requires conversion of the

A test kit for the presence ofglucose in urine.

a form to the 13 form. Fortunately, this interconversionis rapid and complete in the short time required forthe test.

Molecular oxygen, 02' is the oxidizing agent in thisreaction and is reduced to hydrogen peroxide, H 20 2In one procedure, hydrogen peroxide formed in theglucose oxidase-catalyzed reaction is used to oxidizecolorless o-toluidine to a colored product in a reactioncatalyzed by the enzyme peroxidase. The concentrationof the colored oxidation product is determined spectro-photometrically and is proportional to the concentra-tion of glucose in the test solution.

aCH' + H,O, --,p~e_ro_x_idas_e~) colored product2-Methylaniline(0-Toluidine)

Several commercially available test kits use the glucoseoxidase reaction for qualitative determination of glucosein urine.

only at one site in the molecule. The fructoside, therefore, must be a five-memberedring (a fructofuranoside) .

HHO

Periodic acid cleavesonly this bond

Methyl f:'-n-fructofuranoside

25.4 Disaccharides and OligosaccharidesMost carbohydrates in nature contain more than one monosaccharide unit.Those that contain two units are called disaccharides, those that contain threeunits are called trisaccharides, and so forth. The general term oligosaccharide is

DisaccharideA carbohydrate containing twomonosaccharide units joined by aglycosidic bond.OligosaccharideA carbohydrate containing four toten monosaccharide units, eachjoined to the next by a glycosidicbond.

25.4 Disaccharides and Oligosaccharides 991

PolysaccharideA carbohydrate containing a largenumber of monosaccharide units,each joined to the next by one ormore glycosidic bonds.

often used for carbohydrates that contain from four to ten monosaccharide units.Carbohydrates containing larger numbers of monosaccharide units are calledpolysaccharides.

In a disaccharide, two monosaccharide units are joined together by a glyco-sidic bond between the anomeric carbon of one unit and an -OH of the other.Three important disaccharides are sucrose, lactose, and maltose.

A. SucroseSucrose (table sugar) is the most abundant disaccharide in the biological world.It is obtained principally from the juice of sugar cane and sugar beets. In sucrose,carbon 1 of a-D-glucopyranose is joined to carbon 2 of ,B-D-fructofuranose by ana-I,2-glycosidic bond.

~CH20HO CH20HOH 1 Ho~a unit of a-n-glucopyranoseHO HO 1--a-I,2-glycosidic bond OHOH ~o 0HOC~20 HOC~20 a unit of J3-n-fructofuranose

HO 2 HO 2CH20H CH20H1 1

HO HO

Sucrose

Note that glucose is a six-membered (pyranose) ring, whereas fructose is a five-membered (furanose) ring. Because the anomeric carbons of both the gluco-pyranose and fructofuranose units are involved in formation of the glycosidicbond, sucrose is a nonreducing sugar.

B. LactoseLactose is the principal sugar present in milk. It makes up about 5-8% of humanmilk and 4-6% of cow's milk. It consists of D-galactopyranose bonded by a,B-I,4-glycosidic bond to carbon 4 ofD-glucopyranose. Lactose is a reducing sugar.

Maltose derives its name from its presence in malt, the juice from sprouted barleyand other cereal grains (from which beer is brewed). Maltose consists of two mole-cules ofD-glucopyranosejoined by an a-I,4-glycosidic bond between carbon 1 (theanomeric carbon) of one unit and carbon 4 of the other unit. Following are repre-

These products help individuals withlactose intolerance meet their calciumneeds.

ci::ii)

~ C. Maltose~@

HO~HOH. J3-I,4-glycosidic bond2 0 j CH20H

:w--0HO 0unit of OH 1 HO OHD-galactose unit of OHn-glucose

Lactose

992 Chapter 25 Carbohydrates

25.5 PolysaccharidesPolysaccharides consist of large numbers of monosaccharide units bonded togetherby glycosidic bonds. Three important polysaccharides, all made up of glucose units,are starch, glycogen, and cellulose.

A. Starch: Amylose and AmylopectinStarch is used for energy storage in plants. It is found in all plant seeds and tubersand is the form in which glucose is stored for later use. Starch can be separatedinto two principal polysaccharides: amylose and amylopectin. Although the starchfrom each plant is unique, most starches contain 20-25% amylose and 75-80%amylopectin.

Complete hydrolysis of both amylose and amylopectin yields only n-glucose.Amylose is composed of unbranched chains of up to 4000 D-glucose unitsjoined bya-l,4-glycosidic bonds. Amylopectin contains chains up to 10,000 n-glucose unitsalso joined by a-l,4-glycosidic bonds. In addition, there is considerable branchingfrom this linear network. At branch points, new chains of 24 to 30 units are startedby a-l,6-glycosidic bonds (Figure 25.4).

B. GlycogenGlycogen is the energy-reserve carbohydrate for animals. Like amylopectin, glycogenis a branched polysaccharide of approximately 106 glucose units joined by a-l,4- and Ja-l,6-glycosidic bonds. The total amount of glycogen in the body of a well-nourished @adult human is about 350 g, divided almost equally between liver and muscle.

C. CelluloseCellulose, the most widely distributed plant skeletal polysaccharide, constitutesalmost half of the cell wall material of wood. Cotton is almost pure cellulose.Cellulose is a linear polysaccharide of n-glucose units joined by f3-l,4-glycosidicbonds (Figure 25.5). It has an average molecular weight of 400,000 g/mol, corre-sponding to approximately 2200 glucose units per molecule. Cellulose moleculesact very much like stiff rods, a feature that enables them to align themselves side byside into well-organized water-insoluble fibers in which the OR groups form numer-ous intermolecular hydrogen bonds. This arrangement of parallel chains in bundlesgives cellulose fibers their high mechanical strength. It is also the reason cellulose isinsoluble in water. When a piece of cellulose-containing material is placed in water,there are not enough water molecules on the surface of the fiber to pull individualcellulose molecules away from the strongly hydrogen-bonded fiber.

1:~CH20HOoHO 1

HO --- a-l,6-glycosidic bond

.... ~CH20Ho 0-OHO 1 I

70 0 4 6CH2 0H~lHOa-l,4-glycosidic 4 CH20H0bonds O~

HOHO

0--

Breads, grains, and pasta aresources ofstarches.

Figure 25.4Amylopectin is a branchedpolymer of approximatelylO,OOO D-glucose units joinedby a-l,4-glycosidic bonds.Branches consist of 24-30n-glucose units started bya-l,6-glycosidic bonds.

25.5 Polysaccharides 995

5. Reduction to Alditols (Section 25.381 Reduction of the carbonyl group of an aldose orketose to a hydroxyl group yields a polyhydroxy compound called an alditol.

CHO CH20H

H OH H OH

HO H NaBH4 l HO H

H OH H OH

H OH H OH

CH20H CH20H

D-Glucose D-Glucitol(D-Sorbitol)

6. Oxidation to an Aldonic Acid (Section 25.3CI Oxidation of the aldehyde group of analdose to a carboxyl group by a mild oxidizing agent gives a polyhydroxycarboxylic acidcalled an aldonic acid.

CHO COOH

H OH H OH

HO H oxidizing HO Hagentl

H OH H OH

H OH H OH

CH20H CH20H

D-Glucose D-Gluconic acid

7. Oxidation by Periodic Acid (Section 25.3EI Periodic acid oxidizes and cleaves carbon-carbon bonds of glycol, a-hydroxyketone, and a-hydroxyaldehyde groups.

CHOHperiodic acid HO~20cleavage at ~ OCHthesetwobonds~ OH 3

Methyl f3 -n-glucopyranoside

PROBLEMSOnline homework for this chapter may be assigned in Organic OWL. indicates problems assignable in Organic OWL.Red numbers indicate applied problems.

Monosaccharides25.7 Explain the meaning of the designations D and L as used to specify the configuration

of monosaccharides.

25.8 How many chiral centers are present in D-glucose? In D-ribose?

25.9 Which carbon of an aldopentose determines whether the pentose has a D or L con-figuration?

25.10 How many aldooctoses are possible? How many D-aldooctoses are possible?

1002 Chapter 25 Carbohydrates Assignable in OWL