chapter 23 carbohydrates

Chapter 23Chapter 23CarbohydratesCarbohydrates

23.123.1Classification of CarbohydratesClassification of Carbohydrates

Classification of Carbohydrates

Monosaccharide

Disaccharide

Oligosaccharide

Polysaccharide

Is not cleaved to a simpler carbohydrate on hydrolysis.

Glucose, for example, is a monosaccharide.

Monosaccharide

Is cleaved to two monosaccharides on hydrolysis.

These two monosaccharides may be the same or different.

Disaccharide

C12H22O11 + H2O

sucrose(a disaccharide)

C6H12O6 + C6H12O6

glucose(a monosaccharide)

fructose(a monosaccharide)

Oligosaccharide:

Gives two or more monosaccharide units on hydrolysis.

Is homogeneous—all molecules of a particularoligosaccharide are the same, including chainlength.

Polysaccharide:

Yields "many" monosaccharide units on hydrolysis.

Mixtures of the same polysaccharide differing onlyin chain length.

Higher Saccharides

No. of carbons Aldose Ketose

4 Aldotetrose Ketotetrose

5 Aldopentose Ketopentose

6 Aldohexose Ketohexose

7 Aldoheptose Ketoheptose

8 Aldooctose Ketooctose

Table 23.1 Some Classes of Carbohydrates

23.223.2Fischer Projections and Fischer Projections and DD,,LL Notation Notation

Fischer Projections

Fischer Projections of Enantiomers

Enantiomers of Glyceraldehyde

(+)-Glyceraldehyde (–)-Glyceraldehyde

23.323.3The AldotetrosesThe Aldotetroses

Stereochemistry assigned on basis of whetherconfiguration of highest-numbered stereogenic center

is analogous to D or L-glyceraldehyde.

An Aldotetrose

D-Erythrose

The Four Aldotetroses

D-Erythrose L-Erythrose

D-Erythrose and L-erythrose are enantiomers.

D-Erythrose D-Threose

D-Erythrose and D-threose are diastereomers.

L-Erythrose D-Threose

L-Erythrose and D-threose are diastereomers.

D-Threose

D-Threose and L-threose are enantiomers.

L-Threose

D-Erythrose L-Erythrose D-Threose L-Threose

23.423.4Aldopentoses and AldohexosesAldopentoses and Aldohexoses

The Aldopentoses

There are 8 aldopentoses.

Four belong to the D-series; four belong to the L-series.

Their names are ribose, arabinose, xylose, and lyxose.

The Four D-Aldopentoses

D-Ribose D-Arabinose D-Xylose D-Lyxose

H OH HO H H OH HHO

H OH H OH HO H HHO

H OH H OH H OH H OH

CH O CH O

Aldohexoses

There are 16 aldopentoses.

8 belong to the D-series; 8 belong to the L-series.

Their names and configurations are best remembered with the aid of the mnemonic described in Section 23.5.

23.523.5A Mnemonic for Carbohydrate A Mnemonic for Carbohydrate

ConfigurationsConfigurations

The Eight D-Aldohexoses

Altruists

Gladly

Gallon

All Allose

Altruists Altrose

Gladly Glucose

Make Mannose

Gum Gulose

In Idose

Gallon Galactose

Tanks Talose

Allose

Altrose

Glucose

Mannose

Gulose

Galactose

Talose

Allose

Altrose

Glucose

Mannose

Gulose

Galactose

Talose

Allose

Altrose

Glucose

Mannose

Gulose

Galactose

Talose

Allose

Altrose

Glucose

Mannose

Gulose

Galactose

Talose

Allose

Altrose

Glucose

Mannose

Gulose

Galactose

Talose

Allose

Altrose

Glucose

Mannose

Gulose

Galactose

Talose

Allose

Altrose

Glucose

Mannose

Gulose

Galactose

Talose

Allose

Altrose

Glucose

Mannose

Gulose

Galactose

Talose

Allose

Altrose

Glucose

Mannose

Gulose

Galactose

Talose

Allose

Altrose

Glucose

Mannose

Gulose

Galactose

Talose

Allose

Altrose

Glucose

Mannose

Gulose

Galactose

Talose

Allose

Altrose

Glucose

Mannose

Gulose

Galactose

Talose

Allose

Altrose

Glucose

Mannose

Gulose

Galactose

Talose

Allose

Altrose

Glucose

Mannose

Gulose

Galactose

Talose

Allose

Altrose

Glucose

Mannose

Gulose

Galactose

Talose

Allose

Altrose

Glucose

Mannose

Gulose

Galactose

Talose

Allose

Altrose

Glucose

Mannose

Gulose

Galactose

Talose

Allose

Altrose

Glucose

Mannose

Gulose

Galactose

Talose

Allose

Altrose

Glucose

Mannose

Gulose

Galactose

Talose

Allose

Altrose

Glucose

Mannose

Gulose

Galactose

Talose

Allose

Altrose

Glucose

Mannose

Gulose

Galactose

Talose

L-Aldohexoses

There are 8 aldohexoses of the L-series.

They have the same name as their mirror image except the prefix is L- rather than D-.

D-(+)-Glucose L-(–)-Glucose

Cyclic Forms of Carbohydrates:

Furanose Forms

Recall from Section 17.8

R"OHC••O ••

R"O C O H••

••

Product is a hemiacetal.

Cyclic Hemiacetals

Aldehydes and ketones that contain an OH group elsewhere in the molecule can undergo intramolecular hemiacetal formation.

The equilibrium favors the cyclic hemiacetal if the ring is 5- or 6-membered.

Equilibrium lies far to the right.

Cyclic hemiacetals that have 5-membered ringsare called furanose forms.

Carbohydrates Form Cyclic Hemiacetals

Stereochemistry is maintained during cyclichemiacetal formation.

D-Erythrose

turn 90°

D-Erythrose

Move O into position by rotating about bond between carbon-3 and carbon-4.

D-Erythrose

4Close ring by hemiacetal formation between OH at C-4 and carbonyl group.

D-Erythrose

Stereochemistry is variable at anomeric carbon;two diastereomers are formed.

D-Erythrose

anomeric carbonCH O

D-Erythrose

-D-Erythrofuranose -D-Erythrofuranose

D-Ribose

Furanose ring formation involves OH group at C-4.

D-Ribose

Need C(3)-C(4) bond rotation to put OH in proper orientation to close 5-membered ring.

CH OHH

H CH2OH

OHOHHO

D-Ribose CH OHH

H CH2OH

OHOHHO

5 CH OHH

D-Ribose

CH2OH group becomes a substituent on ring.

CH OHH

5 HOCH2

-D-Ribofuranose

Cyclic Forms of Carbohydrates:

Pyranose Forms

Cyclic hemiacetals that have 6-membered ringsare called pyranose forms.

Carbohydrates Form Cyclic Hemiacetals

D-Ribose CH OHH

H CH2OH

OHOHHO

Pyranose ring formation involves OH group at C-5.

D-Ribose CH OHH

H CH2OH

OHOHHO

-D-Ribopyranose

D-Ribose H

OHOHHO

-D-Ribopyranose

OHOHHO

-D-Ribopyranose

D-Glucose

CH OHOH

H CH2OH

Pyranose ring formation involves OH group at C-5.

D-Glucose CH OHOH

H CH2OH

CH OHOH

Need C(4)-C(5) bond rotation to put OH in proper orientation to close 6-membered ring.

D-Glucose CH OHOH

-D-Glucopyranose

D-Glucose

-D-Glucopyranose

D-Glucose

-D-Glucopyranose

Pyranose forms of carbohydrates adopt chair conformations.

D-Glucose

-D-Glucopyranose

All substituents are equatorial in -D-glucopyranose.

D-Glucose

-D-Glucopyranose

OH group at anomeric carbon is axialin -D-glucopyranose.

-D-Glucopyranose

D-Ribose

Less than 1% of the open-chain form of D-ribose is present at equilibrium in aqueous solution.

D-Ribose OH

-D-Ribopyranose (56%)

-D-Ribopyranose (20%)

76% of the D-ribose is a mixture of the and - pyranose forms, with the -form predominating.

D-Ribose HOCH2

OHOH H

-D-Ribofuranose (18%)

-D-Ribofuranose (6%)

The and -furanose forms comprise 24% of the mixture.

23.8Mutarotation

Mutarotation

Mutarotation is a term given to the change in the observed optical rotation of a substance with time.

Glucose, for example, can be obtained in either its or -pyranose form. The two forms have different physical properties such as melting point and optical rotation.

When either form is dissolved in water, its initial rotation changes with time. Eventually both solutions have the same rotation.

Mutarotation of D-Glucose

-D-Glucopyranose

Initial: []D +18.7° Initial: []D +112.2°

Final: []D +52.5°

Mutarotation of D-Glucose

-D-Glucopyranose

Explanation: After being dissolved in water, the and forms slowly interconvert via the open-chain form. An equilibrium state is reached that contains 64% and 36% .

23.9Carbohydrate Conformation: The

Anomeric Effect

Pyranose Conformations

The pyranose conformation resembles the chair conformation of cyclohexane in many respects.

Two additional factors should be noted:

1. An equatorial OH is less crowded and better solvated by water than an axial one

2. The anomeric effect

The Anomeric Effect

The anomeric effect stabilizes axial OH and other electronegative groups at the anomeric carbon better than equatorial.

The 36% of the anomer in the equilibrium mixture of glucose is greater than would have been expected based on 1,3-diaxial interactions and the solvation destabilization of the axial OH.

Another Example

The anomeric effect stabilizes the conformational equilibria of pyranoses with an electronegative atom at C-1.

AcOAcO

Origin of the Anomeric Effect is not well understood

Fig. 23.6

23.1023.10KetosesKetoses

Ketoses

Ketoses are carbohydrates that have a ketone carbonyl group in their open-chain form.

C-2 is usually the carbonyl carbon.

Examples

D-Ribulose L-Xylulose D-Fructose

23.1123.11Deoxy SugarsDeoxy Sugars

Deoxy Sugars

Often one or more of the carbons of a carbohydrate will lack an oxygen substituent. Such compounds are called deoxy sugars.

2-Deoxy-D-ribose

Examples

6-Deoxy-L-mannose

23.1223.12Amino SugarsAmino Sugars

Amino Sugars

An amino sugar has one or more of its oxygens replaced by nitrogen.

Example

N-Acetyl-D-glucosamine

Example

L-Daunosamine

23.1323.13Branched-Chain CarbohydratesBranched-Chain Carbohydrates

Branched-Chain Carbohydrates

Carbohydrates that don't have a continuous chain of carbon-carbon bonds are called branched-chain carbohydrates.

Examples

HO CH2OH

D-Apiose

L-Vancosamine

23.1423.14Glycosides: The Fischer Glycosides: The Fischer

GlycosidationGlycosidation

Glycosides

Glycosides have a substituent other than OH at the anomeric carbon.

Usually the atom connected to the anomeric carbon is oxygen.

Example

Linamarin is an O-glycoside derived from D-glucose.

HOCH2 O

HOCH2 CH3

D-Glucose

Glycosides

Glycosides have a substituent other than OH at the anomeric carbon.

Usually the atom connected to the anomeric carbon is oxygen.

Examples of glycosides in which the atom connected to the anomeric carbon is something other than oxygen include S-glycosides (thioglycosides) and N-glycosides (or glycosyl amines).

Example

Adenosine is an N-glycoside derived from D-ribose HOCH2

OHOH H

D-Ribose

Adenosine

Example

Sinigrin is an S-glycoside derived from D-glucose.

D-Glucose O

SCCH2CH

NOSO3K

Glycosides

O-Glycosides are mixed acetals.

O-Glycosides are mixed acetals H

hemiacetal H

OROROH

acetal

Preparation of Glycosides

Glycosides of simple alcohols (such as methanol) are prepared by adding an acid catalyst (usually gaseous HCl) to a solution of a carbohydrate in the appropriate alcohol (the Fischer glycosidation).

Only the anomeric OH group is replaced.

An equilibrium is established between the and -glycosides (thermodynamic control). The more stable stereoisomer predominates.

Preparation of Glycosides

D-Glucose

Preparation of Glycosides O

Methyl-D-glucopyranoside

(major product)(attributed to the anomeric

effect)

Mechanism of Glycoside Formation

Carbocation is stabilized by lone-pair donation from oxygen of the ring.

HOCH2••

•• O

•• ••

Mechanism of Glycoside Formation

•• •• O••

••

HOCH2 •• ••CH3

••+

OHH3C ••

Mechanism of Glycoside Formation O

HOCH2 •• ••CH3

••+

OHH3C ••

••

HOCH2 •• ••

••

–H+ ••

••

23.1523.15DisaccharidesDisaccharides

Disaccharides

Disaccharides are glycosides.

The glycosidic linkage connects two monosaccharides.

Two structurally related disaccharides are cellobiose and maltose. Both are derived from glucose.

Maltose and Cellobiose

Maltose

Maltose is composed of two glucose units linked together by a glycosidic bond between C-1 of one glucose and C-4 of the other.

The stereochemistry at the anomeric carbon of the glycosidic linkage is .

The glycosidic linkage is described as -(14)

HOCH2 HOCH2

OHHOOHHO

HOO O1 4

Cellobiose

Cellobiose is a stereoisomer of maltose.

The only difference between the two is that cellobiose has a -(14) glycosidic bond while that of maltose is -(14).

HOCH2 HOCH2

OHHOOHHO

HOO O1 4

CellobioseMaltose

Cellobiose and Lactose

Cellobiose

Cellobiose and lactose are stereoisomeric disaccharides.

Both have -(14) glycosidic bonds.

The glycosidic bond unites two glucose units in cellobiose. It unites galactose and glucose in lactose.

HOCH2 HOCH2

OHHOOHHO

HOO O1 4

Cellobiose and Lactose

Lactose

Cellobiose and lactose are stereoisomeric disaccharides.

Both have -(14) glycosidic bonds.

The glycosidic bond unites two glucose units in cellobiose. It unites galactose and glucose in lactose.

HOCH2 HOCH2

OHHOOHHO

HOO O1 4

23.1623.16PolysaccharidesPolysaccharides

Cellulose

Cellulose is a polysaccharide composed of several thousand D-glucose units joined by -(14)-glycosidic linkages. Thus, it can also be viewed as a repeating collection of cellobiose units.

Cellulose

Four glucose units of a cellulose chain.

Starch

Starch is a mixture of amylose and amylopectin.

Amylose is a polysaccharide composed of 100 to several thousand D-glucose units joined by -(14)-glycosidic linkages.

Amylose is helical both with respect to the pitch of adjacent glucose units and with respect to the overall chain.

Amylopectin resembles amylose but exhibits branches of 24-30 glucose units linked to the main chain by -(16)-glycosidic bonds.

23.1723.17Reactions of CarbohydratesReactions of Carbohydrates

Carbohydrate Reactivity

Reactions of carbohydrates are similar to other organic reactions we have already studied.

These reactions were once used extensively for structure determination.

Reactions of carbohydrates can involve either open-chain form, furanose, or pyranose form.

23.1823.18Reduction of MonosaccharidesReduction of Monosaccharides

Reduction of Carbohydrates

Carbonyl group of open-chain form is reduced to an alcohol.

Product is called an alditol.

Alditol lacks a carbonyl group so cannot cyclize to a hemiacetal.

Reduction of D-Galactose

-D-galactofuranose

-D-galactopyranose

D-Galactitol (90%)

Reducing agent: NaBH4, H2O(catalytic hydrogenation can also be used)

23.1923.19Oxidation of MonosaccharidesOxidation of Monosaccharides

Oxidation Occurs at the Ends

Easiest to oxidize the aldehyde and the primary alcohol functions.

Aldonic acid Uronic acid Aldaric acid

Aldose

Oxidation of Reducing Sugars

The compounds formed on oxidation of reducing sugars are called aldonic acids.

Aldonic acids exist as lactones when 5- or 6-membered rings can form.

A standard method for preparing aldonic acids uses Br2 as the oxidizing agent.

Oxidation of D-Xylose

D-Xylose

D-Xylonic acid (90%)

Oxidation of D-Xylose

D-Xylonic acid (90%)

OHHOCH2

Uronic Acids

D-Glucuronic acid

Uronic acids contain both an aldehyde and a terminal CO2H function.

Nitric Acid Oxidation

Nitric acid oxidizes both the aldehyde function and the terminal CH2OH of an aldose to CO2H.

The products of such oxidations are called aldaric acids.

Nitric Acid Oxidation

HOHNO3

D-Glucaric acid (41%)D-Glucose

23.2023.20Periodic Acid OxidationPeriodic Acid Oxidation

Recall Periodic Acid Oxidation

Cleavage of a vicinal diol consumes 1 mol of HIO4.

HIO4C O O C+

Section 15.11: Vicinal diols are cleaved by HIO4.

Also Cleaved by HIO4

Cleavage of an -hydroxy carbonyl compound consumes 1 mol of HIO4. One of the products is a carboxylic acid.

HIO4C O O C+

-Hydroxy carbonyl compounds

Also Cleaved by HIO4

2 mol of HIO4 are consumed. 1 mole of formic acid is produced.

HIO4R2C O

R'2C O

Compounds that contain three contiguouscarbons bearing OH groups:

R2C CR'2

Structure Determination Using HIO4

Distinguish between furanose and pyranose formsof methyl arabinoside:

2 vicinal OH groups;consumes 1 mol of HIO4

3 vicinal OH groups;consumes 2 mol of HIO4

23.2123.21Cyanohydrin Formation and Cyanohydrin Formation and

Chain ExtensionChain Extension

Extending the Carbohydrate Chain

Carbohydrate chains can be extended by using cyanohydrin formation as the key step in C—C bond-making.

The classical version of this method is called the Kiliani-Fischer synthesis. The following example is a more modern modification.

-L-arabinofuranose

-L-arabinopyranose

The cyanohydrin is a mixture of two stereoisomers that differ in configuration at C-2; these two diastereomers are separated in the next step.

+separate

L-Mannononitrile L-Gluconononitrile

L-Mannononitrile

H2, H2O

Pd, BaSO4

L-Mannose(56% from L-arabinose)

Likewise...

L-Gluconononitrile

H2, H2O

Pd, BaSO4

L-Glucose(26% from L-arabinose)

23.2223.22Epimerization, Isomerization, Epimerization, Isomerization,

and Retro-Aldol Cleavageand Retro-Aldol Cleavage

Enol Forms of Carbohydrates

Enolization of an aldose scrambles the stereochemistry at C-2.

This process is called epimerization. Diastereomers that differ in stereochemistry at only one of their stereogenic centers are called epimers.

D-Glucose and D-mannose, for example, are epimers.

Epimerization

D-MannoseD-Glucose

Enediol

This equilibration can be catalyzed by hydroxide ion.

Enol Forms of Carbohydrates

The enediol intermediate on the preceding slide can undergo a second reaction. It can lead to the conversion of D-glucose or D-mannose (aldoses) to D-fructose (ketose).

Isomerization

Enediol

D-Glucose orD-Mannose

D-Fructose

Retro-Aldol Cleavage

When D-glucose 6-phosphate undergoes the reaction shown on the preceding slide, the D-fructose that results is formed as its 1,6-diphosphate.

D-Fructose 1,6-diphosphate is cleaved to two 3-carbon products by a reverse aldol reaction.

This retro-aldol cleavage is catalyzed by the enzyme aldolase.

Isomerization

D-Fructose1,6-phosphate

CH2OP(O)(OH)2

aldolase

CH2OP(O)(OH)2

23.2323.23Acylation and Alkylation of Acylation and Alkylation of

Carbohydrate Hydroxyl GroupsCarbohydrate Hydroxyl Groups

Reactivity of Hydroxyl Groups in Carbohydrates

acylationalkylation

Hydroxyl groups in carbohydrates undergo reactions typical of alcohols.

Example: Acylation of -D-Glucopyranose O

+ CH3COCCH3

pyridine O

CH3COCH2

OCH3CO

OOCCH3

Example: Alkylation of Methyl -D-Glucopyranoside O

+ 4CH3I

Ag2O, CH3OH O

CH3OCH3O

CH3OCH2

Classical Method for Ring Size

Ring sizes (furanose or pyranose) have been determined using alkylation as a key step.

CH3OCH3O

CH3OCH2

CH3OCH3O

CH3OCH2

(mixture of + )

OHCH3O

CH3OCH3O

CH3OCH2

(mixture of + )

OHCH3O

CH3OCH3O

CH3OCH2

CH2OCH3

H OCH3

CH2OCH3

H OCH3

This carbon has OHinstead of OCH3.Therefore, its O was theoxygen in the ring.

23.24Glycosides: Synthesis of

Oligosaccharides

Disaccharides

When two carbohydrates combine, both constitutionally isomeric and stereoisomeric pyranosides are possible.

Gentiobiose is a -(16) glycoside of two pyranosyl forms of D-glucose:

Synthesis of Disaccharides

The general strategy involves three stages:

1) Preparation of a suitably protected glycosyl donor and glycosyl acceptor

2)Formation of the glycosidic C-O bond by nucleophilic substitution in which OH group of the glycosyl acceptor acts as the nucleophile toward the anomeric carbon of the donor

3)Removal of the protecting groups

BzOH2C

HO CH2

OAcOAc

BzOH2C

OAcOAc

Glycosyl donor Glycosyl acceptor

For the synthesis of gentiobiose:

AgOSO2CF3

collidine, toluene

Stereoselective for -disaccharide, (Mech. 23.3)

23.25Glycobiology

Glycobiology

Carbohydrates are often covalently bonded to other biomolecules to form a glycoconjugate.

Glycoproteins have one or more oligosaccharides joined covalently via a glycosidic link (O- or N-glycosyl) to a protein

Glycolipids have oligosaccharides that provide a hydrophilic portion to molecules that are generally insoluble in water

Glycobiology is the study of the structure and function of glycoconjugates.

The structure of glycoproteins attached to the surface of blood cells determines where the blood is type A, B, AB, or O.

RN-Acetylgalactosamine

Polymer Protein

OCH2OH

CH3CNH

R R RType A Type B Type O

The structure of glycoproteins attached to the surface of blood cells determines where the blood is type A, B, AB, or O.

Compatibility of blood types is dependent on antigen-antibody interactions. The cell-surface glycoproteins are antigens. Antibodies present in certain blood types can cause the blood cells of certain other types to clump together, thus setting practical limitations on transfusion procedures.

New drugs to treat influenza target an enzyme, neuraminidase, that the virus carries on its surface to remove the coating of N-acetylneuraminic acid before the virus can adhere to and infect a new cell.

HOH3CCHN

OHHOHOH2C

OCO2CH2CH3H2N

H3CCHN

N-acetylneuraminic acid Oseltamivir (Tamiflu) - prodrug

CH3CNH

OHNHCCH3

HO OHCH2OH

PROTEIN

Fig. 23.14 Diagram of a cell-surface glycoprotein, showing the disaccharide unit that is recognized by an invading influenza virus.

N-acetylgalactosamine N-acetylneuraminic acid

chapter 23 carbohydrates

glyceraldehyde glyceraldehyde

monosaccharide units

chain length

carbohydrate configurationsthe

simpler carbohydrate

configuration of highest

numbered stereogenic

classes of carbohydrates23

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