Chapter 22: Carbohydrates

I. 22.1 Introduction
II. 22.2 Monosaccharides
III. 22.3 Mutarotation
IV. 22.4 Glycoside Formation
V. 22.5 Other Reactions of Monosaccharides
VI. 22.6 Oxidation Reactions of Monosaccharides
VII. 22.7 Reduction of Monosaccharides: Alditols
VIII. 22.9 Synthesis and Degradation of
Monosaccharides
IX. 22.10 The D Family of Aldoses
X. 22.12 Disaccharides
XI. 22.13 Polysaccharides
XII. 22.14 Other Biologically Important Sugars
XIII. 22.15 Sugars That Contain Nitrogen

1
I. Introduction
A. Classification of Carbohydrates

• Carbohydrates: “hydrates of carbon”; molecular

formula Cx(H2O)y
• Monosaccharides

CH2OH
O
HO β-D-(+)-Glucose
OH
HO
OH

• Disaccharides: Carbohydrates that undergo

hydrolysis to give 2 monosaccharides

CH2OH
H CH2OH
O O OH
OH
O CH2OH
OH
OH OH

from D-Glucose from D-fructose

(+)-Sucrose
2
• Trisaccharides: hydrolyze to give 3 monosaccharides
• Oligosaccharides: hydrolyze to give 2-10
monosaccharides
• Polysaccharides: hydrolyze to give >10 monosaccharides

B. Functions of Carbohydrates
• Structural support
• Anticoagulants
• Cell-cell recognition
• Photosynthesis

hν
x CO2 + y H2O Cx(H2O)y + x O2

• Energy metabolism

C6H12O6 + 6 O2 6 CO2 + 6 H2O

3
II. Monosaccharides
A. Classification of Monosaccharides
1) Number of carbon atoms in the molecule
2) Whether the monosaccharide contains a keto or
aldehyde group:
3 C atoms: triose 4 C atoms: tetrose
5 C atoms: pentose 6 C atoms: hexose; etc.
O CH2OH
CH C O

CHOH An aldotetrose CHOH A ketopentose

(C4) (C5)
CHOH CHOH

CH2OH CH2OH

B. D and L Designations of Monosaccharides

O
CH2OH
Simplest CH
carbohydrates C O
* CHOH
CH2OH CH2OH
Glyceraldehyde Dihydroxyacetone
4
Glyceraldehyde enantiomers:

O H O H
C C

H OH HO C H
C

CH2OH CH2OH

D-(+)-Glyceraldehyde L-(-)-Glyceraldehyde
R-(+)-Glyceraldehyde S-(-)-Glyceraldehyde

Designate the stereochemistry of longer carbohydrates

in analogy to glyceraldehyde:
O 1 CH2OH
1 CH 2C O
2 CHOH 3 CHOH

3 CHOH 4 CHOH

H OH HO C H
4
C 5

5 CH2OH 6 CH2OH

A D-aldopentose An L-ketohexose
5
C. Structural Formulas for Monosaccharides

Pyranose: six-membered cyclic monosaccharide

Furanose: five-membered cyclic monosaccharide

HO CH2
CH2OH O
OH
O
HO OH
HO OH
CH2OH
OH OH
A D-(+)-Glucopyranose A D-(+)-Fructofuranose

Representations of D-(+)-glucose:

CHO CHO
H OH H C OH
HO H HO C H
H OH H C OH
H OH H C OH
CH2OH CH2OH

Fischer Projection
6
 CH2OH CH2OH
H O H H O OH
H H
OH H OH H
HO OH HO H
H OH H OH
Haworth Formulas

HOCH2 HOCH2
HO O HO O
HO α HO OH
HO HO β
OH
α-D-(+)-glucopyranose β-D-(+)-glucopyranose
Chair Forms

• α- and β-D-(+)-glucopyranose are diastereomers

(also called epimers or anomers):

7
III. Mutarotation
CHO

H OH
CH2OH
HO O HO H
HO H OH
HO
OH
H OH
α-D-(+)-Glucopyranose (36.4%)
mp = 146 oC, [α]D25= +112 CH2OH
D-(+)-Glucose (0.003%)
(open-chain form)

CH2OH
HO O
HO OH
OH
β-D-(+)-Glucopyranose (63.6%)
mp = 150 oC, [α]D25= +18.7

Mechanism:
O H
C
H OH
CH2OH H CH2OH
HO H O O
HO HO
H OH HO O HO OH
OH OH
H OH

CH2OH 8
 IV. Glycoside Formation
O H
C
H OH
CH2OH
HO H HO O CH3OH
HO OH HCl
H OH
OH
H OH

CH2OH
D-glucose

CH2OH CH2OH
O O
HO HO
OCH3
HO HO
HO OH
OCH3
Methyl α-D-glucopyranoside Methyl β-D-glucopyranoside

Glycoside: a carbohydrate acetal

Glucoside: an acetal of glucose

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Mechanism for Acid-Catalyzed Glycoside Formation:

CH2OH CH2OH
HA H -H2O
O O
HO HO
OH -HA O +H2O
HO HO
OH OH H

(a)
CH2OH CH2OH A
H
O H—OCH 3 O
HO HO
O
HO HOCH 3 HO
OH CH3
OH

(b) +HA -HA

HOCH 3 H—OCH 3
CH2OH
O
CH2OH HO
OCH 3
O HO
HO
OH
HO
HO
OCH 3 Methyl
β-D-glucopyranoside
H
+HA -HA A

CH2OH
O
HO
HO
HO
OCH 3

Methyl
α-D-glucopyranoside
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 Salicin is a natural glycoside from willow bark:

CH2OH CH2OH
O
HO
HO O
OH Salicin

Carbohydrate Aglycone

Salicin can be used to synthesize aspirin:

COOH O COOH

HO CH3 CO
(CH3CO)2O
Salicin CH3COOH
H3O+

Salicylic Acid Aspirin

11
 V. Other Reactions of
Monosaccharides
A. Enolization, Tautomerization, and
Isomerization

O H O H O H O H
C C C C
H OH - C OH C OH HO H
OH H2O
HO H HO H HO H HO H
H2O OH
-
H OH H OH H OH H OH
H OH H OH H OH H OH
CH2OH CH2OH CH2OH CH2OH

D-glucose Enolate anion D-mannose

CH2OH HC OH
Enediol
C O tautomer- C OH

HO H ization HO H
H OH H OH
H OH H OH

CH2OH CH2OH

D-Fructose

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 B. Formation of Ethers

CH2OH CH2OH
CH3-OSO3CH3
HO
O
OH- HO
O
HO OCH 3 HO OCH 3
OH O
methyl glucoside

CH2OH CH2OCH 3
HO
O repeated H3CO
O
HO OCH 3 H3CO OCH 3
OCH 3
methylations
OCH 3

Pentamethyl
derivative

• Acetal at C1 can be cleaved with dilute aqueous

acid while the ethers remain intact:

1 CHO
2
H OCH3
CH2OCH3 CH2OCH3
O H3O+ O H3CO
3
H
H3CO H3CO
H3CO OCH3 H2O 4
H3CO OH H OCH3
OCH3 OCH3 5
H OH

CH2OCH3

2,3,4,6-tetra-O-methyl-D-glucose

13
 C. Conversion to Esters
O

CH2OH O CH2O CCH 3

O (CH3CO)2O O
HO CH3 C O
HO pyridine, 0 oC CH3 C O
HO CH3 C O
OH O O CCH 3
O
α-D-Glucopyranose O
α-D-Glucopyranose
pentaethanoate

D. Conversion to Cyclic Acetals

CH3 O
O
CH2OH
HO
CH2OH CH3 O
C
O CH3 CH3 O
+ 2 H2O
HO H2SO4 O
O
HO
OH
CH3
α-D-Galactopyranose CH3

α-D-Galactopyranose
double acetal

Acetonides: acetals formed from acetone

14
VI. Oxidation Reactions of
Monosaccharides
A. Benedict’s and Fehlings Solutions
O CH2OH

CH C O oxidation
Cu2+ (complex) + or Cu2O +
(CHOH)n (CHOH)n products
blue Brick-red
CH2OH CH2OH

Aldose Ketose

Benedict’s solution: complex with citrate in HO-(aq)

Fehling’s solution: complex with tartrate in HO-(aq)

B. Tollen’s Reagent
O CH2OH

Ag+(NH3)2OH- CH C O oxidation
+ or Ag0 +
in H2O (CHOH)n (CHOH)n products
CH2OH CH2OH Silver
Tollen’s mirror
reagent Aldose Ketose

15
 C O O H C O O R
C C
C R' C R'

Reducing sugar Non-reducing sugar

Hemiacetal Acetal
Positive test Negative test

Examples:
CH2OH
HOCH2 H CH2OH
HO O O O OH
OH
HO OH O
CH2OH
OH
HO OH
OH

β-D-(+)-glucopyranose (+)-Sucrose
A reducing sugar A nonreducing sugar

16
 C. Nitric Acid Oxidation

CHO COOH
HNO3
(CH2OH)n (CH2OH)n
CH2OH COOH

Aldose Aldaric acid

Example:
CHO COOH
H OH H OH
HOCH2
HO O HO H HNO3 HO H
HO OH H OH H OH
HO
H OH H OH
CH2OH COOH

D-Glucaric
acid
D-Glucose

17
VII. Reduction of Monosaccharides
O H
CH NaBH4 H COH
or H2/Pt
(CHOH)n (CHOH)n

CH2OH CH2OH
Aldose Alditol

Example:
CHO CH2OH
H OH H OH
CH2OH
O HO H NaBH4 HO H
HO
OH
HO H OH H OH
HO
H OH H OH
β-D-Glucopyranoside
CH2OH CH2OH

D-Glucitol
(D-sorbitol)

18
 VIII. Synthesis and Degradation
of Monosaccharides
A. Kiliani-Fischer Synthesis
H
C O
H C OH

CH2OH
D-(+)-Glyceraldehyde

CN HCN HCN CN
H C OH HO C H To
H C OH
Epimeric
H C OH D-(-)-threose
cyanohydrins
CH2OH CH2OH

1) Ba(OH)2
2) H3O+

COOH CHO
H O Na-Hg, H2O
H C OH O H C OH
H H
H pH 3-5
H C OH H C OH
OH OH
CH2OH CH2OH

Aldonic acid γ-Aldonolactone D-(-)-Erythrose

19
B. The Ruff Degradation
Example:
CHO COOH
CHO
H C OH H C OH
Br2 H2O2 H C OH
H C OH H C OH
H2O Fe2(SO4)3 H C OH
H C OH H C OH
CH2OH
CH2OH CH2OH

D-(-)-Ribose D-(-)-Ribonic acid D-(-)-Erythrose

+ CO2

IX. The D Family of Aldoses

The structures of the C4, C5 and C6 aldoses are
shown in Figure 22.7 on p 1098. Important members
to remember:
D-Glucose D-Mannose
D-Galactose D-Ribose D-Threose
D-Erythrose D-Glyceraldehyde
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 CHO CHO CHO CHO CHO CHO CHO CHO
H OH HO H H OH HO H H OH HO H H OH HO H
H OH H OH HO H HO H H OH H OH HO H HO H
H OH H OH H OH H OH HO H HO H HO H HO H
H OH H OH H OH H OH H OH H OH H OH H OH
CH2OH CH2OH CH2OH CH2OH CH2OH CH2OH CH2OH CH2OH

D-(+)-allose D-(+)-altrose D-(+)-glucose D-(+)-mannose D-(-)-gulose D-(+)-idose D-(+)-galactose D-(+)-talose

CHO CHO CHO CHO

H OH HO H H OH HO H
H OH H OH HO H HO H
H OH H OH H OH H OH
CH2OH CH2OH CH2OH CH2OH
D-(-)-ribose D-(-)-arabinose D-(+)-xylose D-(-)-Lyxose

CHO CHO
H OH HO H
H OH H OH
CH2OH CH2OH
D-(-)-erythrose D-(-)-threose

CHO
H OH
CH2OH
D-(+)-glyceraldehyde 21
X. Disaccharides
A. Sucrose
• Table sugar
• A nonreducing sugar
• Hydrolysis gives one mol each of D-glucose and
D-fructose:

CH2OH
H CH2OH
O O OH
OH
O CH2OH
OH
OH OH

α-glucosidic β-fructosidic
linkage linkage

H3O+

CH2OH CH2OH
H
O O OH
OH HO
OH CH2OH
OH OH
OH
β-D-fructofuranose
α-D-glucopyranose
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 B. Maltose
CH2OH CH2OH
H O H H O OH
H H
OH H OH H
HO O H
H OH H OH

α-glucosidic linkage

HOCH2
HO O
HO
HO HOCH2
O O
HO OH
HO

• 4-O-(α-D-glucopyranosyl)-β-D-glucopyranose
• Gives two mol of D-(+)-glucose on hydrolysis
• A reducing sugar released from starch by diastase
• Mutarotates: α-(+)-maltose, [α]D25 = +168o; β-(+)-maltose,
[α]D25 = +112o; equilibrium mixture, [α]D25 = +136o

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 C. Cellobiose
CH2OH
H O OH
CH2OH H
OH H HOCH2
H O O H HO O HOCH2
H O
OH H H OH HO O
HO H HO HO OH
HO
H OH
β-glucosidic linkage

• 4-O-(β-D-glucopyranosyl)-β-D-glucopyranose
• Produced on partial hydrolysis of cellulose

D. Lactose
CH2OH
H O OH
CH2OH H HO CH OH
OH H 2
HO O O H O HOCH2
H O
OH H H OH HO O
H HO HO OH
H
HO
H OH β-galactosidic linkage

• 4-O-(β-D-galactopyranosyl)-β-D-glucopyranose
• Milk sugar
• A reducing sugar; mutarotates
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XI. Polysaccharides
• Also known as glycans.
• Homopolysaccharides are composed of one type of
monosaccharides.
• Heteropolysaccharides are composed of more than
one type of monosaccharides.

A. Starch
α(1 4) Glucosidic linkage
CH2OH CH2OH
H O H H O
H H
OH H OH H
O O
H OH H OH n

n > 500

• Principle food reserve of plants

• Found in corn, potatoes, wheat and rice.
• Consists of amylose and amylopectin (major
component).
25
 1. Amylopectin

CH2OH CH2OH
H O H H O H
H H
H H
α(1 6) branch
OH OH
O O O
H OH H OH
CH2OH CH2OH CH2OH CH2 CH2OH
H O H H O HH O H H O H H O H
H H H H H
OH H OH H OH H OH H OH H
O O O O O O
H OH H OH H OH H OH H OH

α(1 4)

• Branches every 20-25 glucose units

• High molecular weight; 1– 6 x 106 g mol-1

2. Amylose

• Folds into a left-handed helical secondary structure

• MW 150,000 to 600,000 g mol-1
• Structure is shown in Figure 22.14.

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B. Glycogen

• Glucose polymer that serves as a carbohydrate

reserve for energy metabolism in animals
• Amylopectin serves a similar role in plants.
• Very highly branched (every 6–12 glucose units)
• MW as high as 108 g mol-1

C. Cellulose
β(1 4) Glucosidic linkage
CH2OH
H O O
CH2OH H
OH H
H O O H
H
OH H H OH
H
H OH n

• Cellulose consists of long unbranched polymer

chains of glucose units.
• Chains stack and interact by H-bonding to form
fibrous materials (see Figure 22.17)
27
 XII. Other Biologically Important
Sugars
A. Uronic Acids
CHO CHO
CO2H CO2H
H OH H OH
O HO O
HO H HO H
OH OH OH OH
H OH HO H
HO
H OH H OH
OH OH
CO2H CO2H

D-Glucuronic acid D-Galacturonic acid

B. Ribose and Deoxyribose

HOCH2 CHO HOCH2 CHO
O O
H OH H H
OH OH
H OH H OH
H OH H OH
OH OH CH2OH OH CH2OH

D-Ribose 2-Deoxy-D-ribose

28
XIII. Sugars That Contain Nitrogen
A. Glycosylamines
NH2
N
N
HOCH2 HOCH2
HO O O N N
HO NH2
HO

β-D-Glucopyranosylamine OH OH

Adenosine

B. Amino Sugars
CH2OH
O OH HOCH2
H O
H HO
OH H HO OH
HO H NH2
H NH2

β-D-Glucosamine

29
 CH2OH
O OH HOCH2
H O
H HO
OH H HO OH
HO H
NHCOCH3
H NHCOCH3
N

β-N-Acetyl-D-glucosamine (NAG)

CH2OH
H O O
CH2OH H
OH H
H O O H
H
OH H H NHCOCH3
H
H NHCOCH3 n

Chitin

• Repeating unit of chitin contains N-acetylglucosamines

in β(1 4) linkage.
• Chitin is found is shells of lobsters and crabs and
insect exoskeletens.
30
 CH2OH
O OH HOCH2 CH3
H O
H HO
OR H R = H
RO OH
HO H CO2H
NHCOCH3
H NHCOCH3
N

β-N-Acetylmuramic acid (NAM)

• NAM is a component of bacterial cell walls.

Additional Biologically Important Aminosugars:

• Heparin – prevents clotting of blood (see p 1115)

• RBC cell surface determinants of blood types A,
B and O (see p 1117)
• Streptomycin – antibacterial antibiotics, useful
against penicillin resistant bacteria (see p 1119)

31