Chapter 25. Biomolecules: Chapter 25. Biomolecules: CarbohydratesCarbohydrates

Why this Chapter?Why this Chapter?To see what the structures and 1˚ biological functions of carbohydrates are

To have an introduction on how carbohydrates are biosynthesized and degraded in organisms

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Importance of CarbohydratesImportance of CarbohydratesDistributed widely in natureKey intermediates of metabolism (sugars)Structural components of plants (cellulose)Central to materials of industrial products:

paper, lumber, fibersKey component of food sources: sugars, flour,

vegetable fiberContain OH groups on most carbons in linear

chains or in rings

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Chemical Formula and NameChemical Formula and NameCarbohydrates have roughly as many O’s as C’s

(highly oxidized)Since H’s are about connected to each H and O

the empirical formulas are roughly (C(H2O))n

◦ Appears to be “carbon hydrate” from formulaCurrent terminology: natural materials that

contain many hydroxyls and other oxygen-containing groups

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SourcesSourcesGlucose is produced in plants through

photosynthesis from CO2 and H2OGlucose is converted in plants to other

small sugars and polymers (cellulose, starch)

Dietary carbohydrates provide the major source of energy required by organisms

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25.1 Classification of Carbohydrates25.1 Classification of Carbohydrates Simple sugars (monosaccharides) can't be converted into

smaller sugars by hydrolysis. Carbohydrates are made of two or more simple sugars

connected as acetals (aldehyde and alcohol), oligosaccharides and polysaccharides

Sucrose (table sugar): disaccharide from two monosaccharides (glucose linked to fructose),

Cellulose is a polysaccharide of several thousand glucose units connected by acetal linkages (aldehyde and alcohol)

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Aldoses and KetosesAldoses and Ketosesaldo- and keto- prefixes identify the nature

of the carbonyl group -ose suffix designates a carbohydrateNumber of C’s in the monosaccharide

indicated by root (-tri-, tetra-, penta-, hexa-)

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25.2 Depicting Carbohydrate 25.2 Depicting Carbohydrate Stereochemistry: Fischer ProjectionsStereochemistry: Fischer Projections

Carbohydrates have multiple chirality centers and common sets of atoms

A chirality center C is projected into the plane of the paper and other groups are horizontal or vertical lines

Groups forward from paper are always in horizontal line. The oxidized end of the molecule is always higher on the page (“up”)

The “projection” can be seen with molecular models

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Stereochemical ReferenceStereochemical ReferenceThe reference compounds are the two

enantiomers of glyceraldehyde, C3H6O3A compound is “D” if the hydroxyl group at the

chirality center farthest from the oxidized end of the sugar is on the right or “L” if it is on the left.

D-glyceraldehyde is (R)-2,3-dihydroxypropanal L-glyceraldehyde is (S)-2,3-dihydroxypropanal

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Working With Fischer ProjectionsWorking With Fischer Projections

If groups are not in corresponding positions, they can be exchanged three at a time in rotation – work with molecular models to see how this is done

The entire structure may only be rotated by 180While R, S designations can be deduced from

Fischer projections (with practice), it is best to make molecular models from the projected structure and work with the model

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25.3 25.3 D, LD, L Sugars SugarsGlyceraldehyde exists as two enantiomers, first

identified by their opposite rotation of plane polarized light

Naturally occurring glyceraldehyde rotates plane-polarized light in a clockwise direction, denoted (+) and is designated “(+)-glyceraldehyde”

The enantiomer gives the opposite rotation and has a (-) or “l” (levorotatory) prefix

The direction of rotation of light does not correlate to any structural feature

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Naturally Occurring D Sugars

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25.4 Configurations of the Aldoses25.4 Configurations of the AldosesStereoisomeric aldoses are distinguished by

trivial names, rather than by systematic designations

Enantiomers have the same names but different D,L prefixes

R,S designations are difficult to work with when there are multiple similar chirality centers

Systematic methods for drawing and recalling structures are based on the use of Fischer projections

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Aldotetroses have two chirality centers

There are 4 stereoisomeric aldotetroses, two pairs of enantiomers: erythrose and threose

D-erythrose is a a diastereomer of D-threose and L-threose

Aldopentoses have three chirality centers and 23 = 8 stereoisomers, four pairs of enantiomers: ribose, arabinose, xylose, and lyxose

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25.5 Cyclic Structures of 25.5 Cyclic Structures of Monosaccharides: AnomersMonosaccharides: Anomers

Alcohols add reversibly to aldehydes and ketones, forming hemiacetals

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Internal Hemiacetals of SugarsInternal Hemiacetals of Sugars Intramolecular nucleophilic addition creates

cyclic hemiacetals in sugars Five- and six-membered cyclic hemiacetals are

particularly stable Five-membered rings are furanoses. Six-

membered are pyanoses Formation of the the cyclic hemiacetal creates an

additional chirality center giving two diasteromeric forms, designated and

These diastereomers are called anomers The designation indicates that the OH at the

anomeric center is on the same side of the Fischer projection structure as hydroxyl that designates whether the structure us D or L

Converting to Proper StructuresConverting to Proper Structures The Fischer

projection structures must be redrawn to consider real bond lengths, and you also see the “Pyran” form

Pyranose rings have a chair-like geometry with axial and equatorial substituents

Rings are usually drawn placing the hemiacetal oxygen atom at the right rear

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Monosaccharide Anomers: Monosaccharide Anomers: MutarotationMutarotation

The two anomers of D-glucopyranose can be crystallized and purified◦ -D-glucopyranose melts at 146° and its specific

rotation, []D = 112.2°;◦ -D-glucopyranose melts at 148–155°C with a specific

rotation of []D = 18.7°Rotation of solutions of either pure anomer slowly

changes due to slow conversion of the pure anomers into a 37:63 equilibrium mixture of : called mutarotation

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25.6 Reactions of Monosaccharides25.6 Reactions of Monosaccharides

OH groups can be converted into esters and ethers, which are often easier to work with than the free sugars and are soluble in organic solvents.◦ Esterification by treating with an acid chloride or

acid anhydride in the presence of a base◦ All OH groups react

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EthersEthers

Treatment with an alkyl halide in the presence of base—the Williamson ether synthesis

Use silver oxide as a catalyst with base-sensitive compounds

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Glycoside FormationGlycoside Formation

Treatment of a monosaccharide hemiacetal with an alcohol and an acid catalyst yields an acetal in which the anomeric OH has been replaced by an OR group◦ -D-glucopyranose with methanol and acid gives

a mixture of and methyl D-glucopyranosides

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GlycosidesGlycosides

Carbohydrate acetals are named by first citing the alkyl group and then replacing the -ose ending of the sugar with –oside

Stable in water, requiring acid for hydrolysis

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Selective Formation of C1-AcetalSelective Formation of C1-Acetal

Synthesis requires distinguishing the numerous OH groups

Treatment of glucose pentaacetate with HBr converts anomeric OH to Br

Addition of alcohol (with Ag2O) gives a glycoside (Koenigs–Knorr reaction)

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Koenigs-Knorr Reaction MechanismKoenigs-Knorr Reaction Mechanism and anomers of tetraacetyl-D-

glucopyranosyl bromide give -glycosideSuggests either bromide leaves and cation is

stabilized by neighboring acetyl nucleophile from side

Incoming alcohol displaces acetyl oxygen to give glycoside

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Reduction of MonosaccharidesReduction of Monosaccharides

Treatment of an aldose or ketose with NaBH4 reduces it to a polyalcohol (alditol)

Reaction via the open-chain form in the aldehyde/ketone hemiacetal equilibrium

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Oxidation of MonosaccharidesOxidation of MonosaccharidesAldoses are easily oxidized to carboxylic acids

by: Tollens' reagent (Ag+, NH3), Fehling's reagent (Cu2+, sodium tartrate), Benedict`s reagent (Cu2+ sodium citrate)◦ Oxidations generate metal mirrors; serve as tests

for “reducing” sugars (produce metallic mirrors)Ketoses are reducing sugars if they can

isomerize to aldoses

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Oxidation of MonosaccharidesOxidation of Monosaccharideswith Brominewith Bromine

Br2 in water is an effective oxidizing reagent for converting aldoses to carboxylic acid, called aldonic acids (the metal reagents are for analysis only)

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Formation of Dicarboxylic AcidsFormation of Dicarboxylic Acids

Warm dilute HNO3 oxidizes aldoses to dicarboxylic acids, called aldaric acids

The CHO group and the terminal CH2OH group are oxidized to COOH

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Chain Lengthening: The Kiliani–Fischer Chain Lengthening: The Kiliani–Fischer SynthesisSynthesis Lengthening aldose chain by one CH(OH), (ie. aldopentose aldohexose Aldoses form cyanohydrins with HCN

◦ Follow by hydrolysis, ester formation, reduction

Modern improvement: reduce nitrile over a palladium catalyst, yielding an imine intermediate that is hydrolyzed to an aldehyde

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Stereoisomers from Kiliani-Fischer Stereoisomers from Kiliani-Fischer SynthesisSynthesis

Cyanohydrin is formed as a mixture of stereoisomers at the new chirality center, resulting in two aldoses

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Chain Shortening: The Wohl DegradationChain Shortening: The Wohl Degradation

Shortens aldose chain by one CH2OH

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25.7 The Eight Essential Monosaccharides25.7 The Eight Essential Monosaccharides

Cells need eight monosaccharides for proper functioning

More energetically efficient to obtain these from environment1. L-fucose, 2. D-galactose, 3. D-glucose, 4. D-mannose, 5. N-acetyl-D-glucosamine, 6. N-acetyl-D-galactosamine, 7. D-xylose, 8. N-acetyl-D-neuraminic acid

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25.8 Disaccharides25.8 Disaccharides

A disaccharide combines a hydroxyl of one monosaccharide in an acetal linkage with another

A glycosidic bond between C1 of the first sugar ( or ) and the OH at C4 of the second sugar is particularly common (a 1,4 link)

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Maltose and CellobioseMaltose and CellobioseMaltose: two D-

glucopyranose units witha 1,4--glycoside bond (from starch hydrolysis)

Cellobiose: two D-glucopyranose units with a1,4--glycoside bond (from cellulose hydrolysis)

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Hemiacetals in DisaccharidesHemiacetals in Disaccharides

Maltose and cellobiose are both reducing sugarsThe and anomers equilibrate, causing

mutarotation

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LactoseLactoseA disaccharide that occurs naturally in milkLactose is a reducing sugar. It exhibits

mutarotation It is 1,4’--D-galactopyranosyl-D-glucopyranosideThe structure is cleaved in digestion to glucose

and galactose

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SucroseSucrose“Table Sugar” is pure sucrose, a disaccharide

that hydrolyzes to glucose and fructoseNot a reducing sugar and does not undergo

mutarotation (not a hemiacetal)Connected as acetal from both anomeric

carbons (aldehyde to ketone)

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25.9 Polysaccharides and Their Synthesis25.9 Polysaccharides and Their Synthesis

Complex carbohydrates in which very many simple sugars are linked

Cellulose and starch are the two most widely occurring polysaccharides

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CelluloseCellulose

Consists of thousands of D-glucopyranosyl 1,4--glucopyranosides as in cellobiose

Cellulose molecules form a large aggregate structures held together by hydrogen bonds

Cellulose is the main component of wood and plant fiber

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Starch and GlycogenStarch and GlycogenStarch is a 1,4--glupyranosyl-glucopyranoside

polymer It is digested into glucoseThere are two components

◦ amylose, insoluble in water – 20% of starch 1,4’--glycoside polymer

◦ amylopectin, soluble in water – 80% of starch

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AmylopectinAmylopectinMore complex in structure than amyloseHas 1,6--glycoside branches approximately

every 25 glucose units in addition to 1,4--links

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GlycogenGlycogenA polysaccharide that serves the same energy

storage function in animals that starch serves in plants

Highly branched and larger than amylopectin—up to 100,000 glucose units

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Synthesis of Polysaccharides – via GlycalsSynthesis of Polysaccharides – via Glycals

Difficult to do efficiently, due to many OH groupsGlycal assembly is one approach to being selectiveProtect C6 OH as silyl ether, C3OH and C4OH

as cyclic carbonateGlycal C=C is converted to epoxide

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Glycal CouplingGlycal CouplingReact glycal epoxide with a second glycal having a

free OH (with ZnCl2 catayst) yields a disaccharide

The disaccharide is a glycal, so it can be epoxidized and coupled again to yield a trisaccharide, and then extended

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25.10 Other Important Carbohydrates25.10 Other Important Carbohydrates

Deoxy sugars have an OH group is replaced by an H.◦ Derivatives of 2-deoxyribose are the fundamental

units of DNA (deoxyribonucleic acid)

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Amino SugarsAmino SugarsOH group is replaced by an NH2Amino sugars are found in antibiotics such as

streptomycin and gentamicin

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25.11 Cell-Surface Carbohydrates and 25.11 Cell-Surface Carbohydrates and Carbohydrate VaccinesCarbohydrate Vaccines

Polysaccharides are centrally involved in cell–cell recognition - how one type of cell distinguishes itself from another

Small polysaccharide chains, covalently bound by glycosidic links to hydroxyl groups on proteins (glycoproteins), act as biochemical markers on cell surfaces, determining such things as blood type

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Which of the following best Which of the following best describes the molecule shown describes the molecule shown below:below:

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20% 20% 20%20%20%

1. monosaccharide2. pentose3. aldose4. all of these5. none of these

How many stereoisomers are How many stereoisomers are possible for the aldotetrose class of possible for the aldotetrose class of carbohydrates?carbohydrates?

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1. one2. two3. three4. four5. five

Which of the following sugars is the Which of the following sugars is the key carbohydrate energy-reserve in key carbohydrate energy-reserve in plants?plants?

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1. glucose2. glycogen3. cellulose4. maltose5. lactose

All carbohydrates have the All carbohydrates have the general formula Cgeneral formula CnnHH2n2nOOnn..

1 2

50%50%

1. True2. False

Which of the following statements is true Which of the following statements is true concerning the carbohydrate shown concerning the carbohydrate shown below:below:

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1. Carbon 4 is part of a secondary alcohol.

2. The absolute configuration of carbon 2 is (R).

3. The absolute configuration of carbon 3 is (S).

4. The molecule is achiral.5. None of these

statements is true.

Which of the following disaccharides Which of the following disaccharides is also known as table sugar?is also known as table sugar?

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1. lactose2. fructose3. maltose4. glucose5. sucrose

5.

2.

Which of the following is a D-Which of the following is a D-ketohexose?ketohexose?

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1.

3.

4.

Which of the following statements Which of the following statements is is falsefalse concerning the aldohexose, concerning the aldohexose, D-mannose?D-mannose?

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20% 20% 20%20%20%1. The carbohydrate can

exist as a furanose.2. The carbohydrate can

exist as a pyranose.3. The cyclic form of the

sugar is an acetal.4. The cyclic form of the

sugar possesses an anomeric carbon.

5. The cyclic form of the molecule is chiral.

The following structure The following structure represents the β-anomer of D-represents the β-anomer of D-galactose:galactose:

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1. True2. False

O

HO

HOOH

OH

OH

Which of the following open-chain forms Which of the following open-chain forms would lead to the cyclic pyranose shown would lead to the cyclic pyranose shown below?below?

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CHO

HHO

HHO

HHO

OHH

CH2OH

1.CHO

OHH

HHO

HHO

OHH

CH2OH

2.

CHO

OHH

OHH

HHO

OHH

CH2OH

3.

CHO

OHH

HHO

OHH

OHH

CH2OH

4.CHO

OHH

HHO

HHO

HHO

CH2OH

5.

OHO

OH

OH

OH

OH

[ open chain form ]

CHO

OHH

OHH

OHH

OHH

CH2OH

A glycoside is not a reducing A glycoside is not a reducing sugar when subjected to the sugar when subjected to the Tollens' test.Tollens' test.

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1. True2. False

Which choice best describes the Which choice best describes the sugar shown below:sugar shown below:

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1. α-furanose of ribose2. β-furanose of ribose3. α-furanose of

arabinose4. β-pyranose of

arabinose5. α-furanose of

lyxose

Which term best describes the Which term best describes the disaccharide shown below:disaccharide shown below:

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1. α-1,3-disaccharide2. β-1,3-disaccharide3. α-1,4-disaccharide4. β-1,4-disaccharide5. none of these

The label has fallen off a bottle that contains a sugar with The label has fallen off a bottle that contains a sugar with the formula Cthe formula C66HH1212OO66. Oxidation of the unknown sugar at . Oxidation of the unknown sugar at both ends gives an optically active dicarboxylic acid, both ends gives an optically active dicarboxylic acid, AA. The . The β-pyranose of the unknown sugar is found to contain two β-pyranose of the unknown sugar is found to contain two axial substituents. Select the structure that represents the axial substituents. Select the structure that represents the original sugar in the bottle.original sugar in the bottle.

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20% 20% 20%20%20%1. 2.

3.

4. 5.

CHO

HHO

HHO

OHH

OHH

CH2OH

An aldohexose, An aldohexose, AA, is reacted with Br, is reacted with Br22/H/H22O to yield an aldonic O to yield an aldonic acid, acid, BB. The other end of . The other end of BB is oxidized to yield an optically is oxidized to yield an optically active sugar, active sugar, CC. Reaction of . Reaction of CC with one equivalent of LiAlH with one equivalent of LiAlH44 in Etin Et22O followed by workup with HO followed by workup with H22O results in only one O results in only one unique product, unique product, DD. Of the eight naturally occurring D-. Of the eight naturally occurring D-aldohexoses, how many can satisfy the conditions of this aldohexoses, how many can satisfy the conditions of this problem?problem?

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1. 12. 23. 34. 45. 5