Chapter 23 Carbohydrates

1
Chapter 23Carbohydrates
2
23.1Classification of Carbohydrates
3
Classification of Carbohydrates

• Monosaccharide
• Disaccharide
• Oligosaccharide
• Polysaccharide

4
Monosaccharide

• Is not cleaved to a simpler carbohydrate on
  hydrolysis.
• Glucose, for example, is a monosaccharide.

5
Disaccharide

• Is cleaved to two monosaccharides on hydrolysis.
• These two monosaccharides may be the same or
  different.

C12H22O11 H2O
sucrose(a disaccharide)
6
Higher Saccharides

• Oligosaccharide
• Gives two or more monosaccharide units on
  hydrolysis. Is homogeneousall molecules of a
  particular oligosaccharide are the same,
  including chain length.
• Polysaccharide
• Yields "many" monosaccharide units on
  hydrolysis. Mixtures of the same polysaccharide
  differing only in chain length.

7
Table 23.1 Some Classes of Carbohydrates

• No. of carbons Aldose Ketose
• 4 Aldotetrose Ketotetrose
• 5 Aldopentose Ketopentose
• 6 Aldohexose Ketohexose
• 7 Aldoheptose Ketoheptose
• 8 Aldooctose Ketooctose

8
23.2Fischer Projections and D,L Notation
9
Fischer Projections
10
Fischer Projections
11
Fischer Projections of Enantiomers
12
Enantiomers of Glyceraldehyde
()-Glyceraldehyde
()-Glyceraldehyde
13
23.3The Aldotetroses
14
An Aldotetrose
1
2
3
4

• Stereochemistry assigned on basis of
  whetherconfiguration of highest-numbered
  stereogenic centeris analogous to D or
  L-glyceraldehyde.

15
An Aldotetrose
1
2
3
4
D-Erythrose
16
The Four Aldotetroses

• D-Erythrose and L-erythrose are enantiomers.

D-Erythrose
L-Erythrose
17
The Four Aldotetroses

• D-Erythrose and D-threose are diastereomers.

D-Erythrose
D-Threose
18
The Four Aldotetroses

• L-Erythrose and D-threose are diastereomers.

L-Erythrose
D-Threose
19
The Four Aldotetroses

• D-Threose and L-threose are enantiomers.

HO
L-Threose
D-Threose
20
The Four Aldotetroses
HO
D-Erythrose
L-Erythrose
D-Threose
L-Threose
21
23.4Aldopentoses and Aldohexoses
22
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.

23
The Four D-Aldopentoses
D-Ribose
D-Arabinose
D-Xylose
D-Lyxose
24
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.

25
23.5A Mnemonic for Carbohydrate Configurations
26
The Eight D-Aldohexoses
27
The Eight D-Aldohexoses

• All
• Altruists
• Gladly
• Make
• Gum
• In
• Gallon
• Tanks

28
The Eight D-Aldohexoses

• All Allose
• Altruists Altrose
• Gladly Glucose
• Make Mannose
• Gum Gulose
• In Idose
• Gallon Galactose
• Tanks Talose

29
The Eight D-Aldohexoses

• Allose
• Altrose
• Glucose
• Mannose
• Gulose
• Idose
• Galactose
• Talose

30
The Eight D-Aldohexoses

• Allose
• Altrose
• Glucose
• Mannose
• Gulose
• Idose
• Galactose
• Talose

31
The Eight D-Aldohexoses

• Allose
• Altrose
• Glucose
• Mannose
• Gulose
• Idose
• Galactose
• Talose

32
The Eight D-Aldohexoses

• Allose
• Altrose
• Glucose
• Mannose
• Gulose
• Idose
• Galactose
• Talose

33
The Eight D-Aldohexoses

• Allose
• Altrose
• Glucose
• Mannose
• Gulose
• Idose
• Galactose
• Talose

34
The Eight D-Aldohexoses

• Allose
• Altrose
• Glucose
• Mannose
• Gulose
• Idose
• Galactose
• Talose

35
The Eight D-Aldohexoses

• Allose
• Altrose
• Glucose
• Mannose
• Gulose
• Idose
• Galactose
• Talose

36
The Eight D-Aldohexoses

• Allose
• Altrose
• Glucose
• Mannose
• Gulose
• Idose
• Galactose
• Talose

37
The Eight D-Aldohexoses

• Allose
• Altrose
• Glucose
• Mannose
• Gulose
• Idose
• Galactose
• Talose

38
The Eight D-Aldohexoses

• Allose
• Altrose
• Glucose
• Mannose
• Gulose
• Idose
• Galactose
• Talose

39
The Eight D-Aldohexoses

• Allose
• Altrose
• Glucose
• Mannose
• Gulose
• Idose
• Galactose
• Talose

40
The Eight D-Aldohexoses

• Allose
• Altrose
• Glucose
• Mannose
• Gulose
• Idose
• Galactose
• Talose

41
The Eight D-Aldohexoses

• Allose
• Altrose
• Glucose
• Mannose
• Gulose
• Idose
• Galactose
• Talose

42
The Eight D-Aldohexoses

• Allose
• Altrose
• Glucose
• Mannose
• Gulose
• Idose
• Galactose
• Talose

43
The Eight D-Aldohexoses

• Allose
• Altrose
• Glucose
• Mannose
• Gulose
• Idose
• Galactose
• Talose

44
The Eight D-Aldohexoses

• Allose
• Altrose
• Glucose
• Mannose
• Gulose
• Idose
• Galactose
• Talose

45
The Eight D-Aldohexoses

• Allose
• Altrose
• Glucose
• Mannose
• Gulose
• Idose
• Galactose
• Talose

46
The Eight D-Aldohexoses

• Allose
• Altrose
• Glucose
• Mannose
• Gulose
• Idose
• Galactose
• Talose

47
The Eight D-Aldohexoses

• Allose
• Altrose
• Glucose
• Mannose
• Gulose
• Idose
• Galactose
• Talose

48
The Eight D-Aldohexoses

• Allose
• Altrose
• Glucose
• Mannose
• Gulose
• Idose
• Galactose
• Talose

49
The Eight D-Aldohexoses

• Allose
• Altrose
• Glucose
• Mannose
• Gulose
• Idose
• Galactose
• Talose

50
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
51
23.6Cyclic Forms of CarbohydratesFuranose Forms
52
Recall from Section 17.8

R"OH

• Product is a hemiacetal.

53
Cyclic Hemiacetals
R
OH
C
O

• 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.

54
Carbohydrates Form Cyclic Hemiacetals
1
2
3
4

• Equilibrium lies far to the right.
• Cyclic hemiacetals that have 5-membered ringsare
  called furanose forms.

55
D-Erythrose
1
H
H
H
2
H
OH
3
H
OH
H
OH
OH
4

• Stereochemistry is maintained during
  cyclichemiacetal formation.

56
D-Erythrose
1
2
3
4
57
D-Erythrose

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

1
4
2
3
58
D-Erythrose
1
1
4
4
2
2
3
3
59
D-Erythrose

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

1
4
2
3
60
D-Erythrose
1
1
4
4
2
2
3
3
61
D-Erythrose
anomeric carbon
1
H
H
H
2
H
OH
3
H
OH
H
OH
OH
4

• Stereochemistry is variable at anomeric
  carbontwo diastereomers are formed.

62
D-Erythrose
H
H
H
H
H
H
H
H
OH
OH
OH
OH
?-D-Erythrofuranose
?-D-Erythrofuranose
63
D-Ribose

• Furanose ring formation involves OH group at C-4.

64
D-Ribose

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

65
D-Ribose
66
D-Ribose
?-D-Ribofuranose

• CH2OH group becomes a substituent on ring.

67
23.7Cyclic Forms of CarbohydratesPyranose Forms
68
Carbohydrates Form Cyclic Hemiacetals
5
OH
O
1
4
H
2
3

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

69
D-Ribose

• Pyranose ring formation involves OH group at C-5.

70
D-Ribose
71
D-Ribose
?-D-Ribopyranose
?-D-Ribopyranose
72
D-Glucose

• Pyranose ring formation involves OH group at C-5.

73
D-Glucose

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

74
D-Glucose
?-D-Glucopyranose
75
D-Glucose
?-D-Glucopyranose
?-D-Glucopyranose
76
D-Glucose
?-D-Glucopyranose

• Pyranose forms of carbohydrates adopt chair
  conformations.

77
D-Glucose
6
HOCH2
6
5
OH
H
4
O
5
H
1
4
H
OH
2
3
HO
1
H
2
3
OH
H
?-D-Glucopyranose

• All substituents are equatorial in
  ?-D-glucopyranose.

78
D-Glucose
1
1
?-D-Glucopyranose
?-D-Glucopyranose

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

79
D-Ribose

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

80
D-Ribose

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

81
D-Ribose

• The ? and ?-furanose forms comprise 24 of the
  mixture.

?-D-Ribofuranose (18)
?-D-Ribofuranose (6)
82
23.8Mutarotation
83
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.

84
Mutarotation of D-Glucose
1
1
?-D-Glucopyranose
?-D-Glucopyranose
Initial ?D 18.7
Initial ?D 112.2
85
Mutarotation of D-Glucose
1
1
?-D-Glucopyranose
?-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 ?.

86
23.9Carbohydrate Conformation The Anomeric
Effect
87
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

88
The Anomeric Effect

• The anomeric effect stabilizes axial OH and other
  electronegative groups at the anomeric carbon
  better than equatorial.
• The 36 of the a-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.

89
Another Example

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

98
2
90
Origin of the Anomeric Effect is not well
understood

• Fig. 23.6

91
23.10Ketoses
92
Ketoses

• Ketoses are carbohydrates that have a ketone
  carbonyl group in their open-chain form.
• C-2 is usually the carbonyl carbon.

93
Examples
D-Ribulose
L-Xylulose
D-Fructose
94
23.11Deoxy Sugars
95
Deoxy Sugars

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

96
Examples
2-Deoxy-D-ribose
6-Deoxy-L-mannose
97
23.12Amino Sugars
98
Amino Sugars

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

99
Example
N-Acetyl-D-glucosamine
100
Example
L-Daunosamine
101
23.13Branched-Chain Carbohydrates
102
Branched-Chain Carbohydrates

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

103
Examples
D-Apiose
L-Vancosamine
104
23.14Glycosides The Fischer Glycosidation
105
Glycosides

• Glycosides have a substituent other than OH at
  the anomeric carbon.
• Usually the atom connected to the anomeric carbon
  is oxygen.

106
Example
D-Glucose

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

107
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).

108
Example

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

D-Ribose
Adenosine
109
Example
D-Glucose

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

110
Glycosides

• O-Glycosides are mixed acetals.

111
O-Glycosides are mixed acetals
hemiacetal
112
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.

113
Preparation of Glycosides
CH3OH
HCl
D-Glucose
114
Preparation of Glycosides
Methyl?-D-glucopyranoside

Methyl?-D-glucopyranoside(major
product) (attributed to the anomeric effect)
115
Mechanism of Glycoside Formation
HCl

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

116
Mechanism of Glycoside Formation

117
Mechanism of Glycoside Formation


118
23.15Disaccharides
119
Disaccharides

• Disaccharides are glycosides.
• The glycosidic linkage connects two
  monosaccharides.
• Two structurally related disaccharides are
  cellobiose and maltose. Both are derived from
  glucose.

120
Maltose and Cellobiose
?
Maltose
1
4

• 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 ?-(1?4)

121
Maltose and Cellobiose
?
Cellobiose

• Cellobiose is a stereoisomer of maltose.
• The only difference between the two is that
  cellobiose has a ?-(1?4) glycosidic bond while
  that of maltose is ?-(1?4).

122
Maltose and Cellobiose
Cellobiose
Maltose
123
Cellobiose and Lactose
?
Cellobiose

• Cellobiose and lactose are stereoisomeric
  disaccharides.
• Both have ?-(1?4) glycosidic bonds.
• The glycosidic bond unites two glucose units in
  cellobiose. It unites galactose and glucose in
  lactose.

124
Cellobiose and Lactose
Lactose

• Cellobiose and lactose are stereoisomeric
  disaccharides.
• Both have ?-(1?4) glycosidic bonds.
• The glycosidic bond unites two glucose units in
  cellobiose. It unites galactose and glucose in
  lactose.

125
23.16Polysaccharides
126
Cellulose

• Cellulose is a polysaccharide composed of several
  thousand D-glucose units joined by
  ?-(1?4)-glycosidic linkages. Thus, it can also
  be viewed as a repeating collection of cellobiose
  units.

127
Cellulose
Four glucose units of a cellulose chain.
128
Starch

• Starch is a mixture of amylose and amylopectin.
• Amylose is a polysaccharide composed of 100 to
  several thousand D-glucose units joined by
  ?-(1?4)-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 ?-(1?6)-glycosidic bonds.

129
23.17Reactions of Carbohydrates
130
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.

131
23.18Reduction of Monosaccharides
132
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.

133
Reduction of D-Galactose
Reducing agent NaBH4, H2O(catalytic
hydrogenation can also be used)
134
23.19Oxidation of Monosaccharides
135
Oxidation Occurs at the Ends

• Easiest to oxidize the aldehyde and the primary
  alcohol functions.

Uronic acid
Aldaric acid
Aldonic acid
Aldose
136
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.

137
Oxidation of D-Xylose
D-Xylose
138
Oxidation of D-Xylose

D-Xylonic acid (90)
139
Uronic Acids

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

140
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.

141
Nitric Acid Oxidation
HNO3
60C
D-Glucose
142
23.20Periodic Acid Oxidation
143
Recall Periodic Acid Oxidation
Section 15.11 Vicinal diols are cleaved by HIO4.

• Cleavage of a vicinal diol consumes 1 mol of HIO4.

144
Also Cleaved by HIO4
?-Hydroxy carbonyl compounds
R
O

C
RC
C
HO
OH

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

145
Also Cleaved by HIO4
Compounds that contain three contiguouscarbons
bearing OH groups

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

146
Structure Determination Using HIO4
Distinguish between furanose and pyranose
formsof methyl arabinoside
2 vicinal OH groupsconsumes 1 mol of HIO4
3 vicinal OH groupsconsumes 2 mol of HIO4
147
23.21Cyanohydrin Formation and Chain Extension
148
Extending the Carbohydrate Chain

• Carbohydrate chains can be extended by using
  cyanohydrin formation as the key step in CC
  bond-making.
• The classical version of this method is called
  the Kiliani-Fischer synthesis. The following
  example is a more modern modification.

149
Extending the Carbohydrate Chain
HCN

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

150
Extending the Carbohydrate Chain
separate

L-Mannononitrile
L-Gluconononitrile
151
Extending the Carbohydrate Chain
L-Mannononitrile
152
Likewise...
L-Gluconononitrile
153
23.22Epimerization, Isomerization, and
Retro-Aldol Cleavage
154
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.

155
Epimerization
D-Mannose
D-Glucose
This equilibration can be catalyzed by hydroxide
ion.
156
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).

157
Isomerization
Enediol
158
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.

159
Isomerization
D-Fructose1,6-phosphate
160
23.23Acylation and Alkylation of Carbohydrate
Hydroxyl Groups
161
Reactivity of Hydroxyl Groups in Carbohydrates
Hydroxyl groups in carbohydrates undergo
reactions typical of alcohols.

• acylationalkylation

162
Example Acylation of ?-D-Glucopyranose
O
O
CH3COCCH3
5

163
Example Alkylation of Methyl ?-D-Glucopyranoside
4CH3I

164
Classical Method for Ring Size
Ring sizes (furanose or pyranose) have been
determined using alkylation as a key step.
165
Classical Method for Ring Size
Ring sizes (furanose or pyranose) have been
determined using alkylation as a key step.
H2O
H
(mixture of ? ?)
166
Classical Method for Ring Size
Ring sizes (furanose or pyranose) have been
determined using alkylation as a key step.
(mixture of ? ?)
167
Classical Method for Ring Size
Ring sizes (furanose or pyranose) have been
determined using alkylation as a key step.
This carbon has OHinstead of OCH3.Therefore,
its O was theoxygen in the ring.
168
23.24Glycosides Synthesis of Oligosaccharides
169
Disaccharides

• When two carbohydrates combine, both
  constitutionally isomeric and stereoisomeric
  pyranosides are possible.
• Gentiobiose is a b-(1?6) glycoside of two
  pyranosyl forms of D-glucose

b
1
6
170
Synthesis of Disaccharides

• The general strategy involves three stages
• 1) Preparation of a suitably protected glycosyl
  donor and glycosyl acceptor
• 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
• Removal of the protecting groups

171
For the synthesis of gentiobiose
Glycosyl donor
Glycosyl acceptor
AgOSO2CF3 collidine, toluene
Stereoselective for b-disaccharide, (Mech. 23.3)
172
23.25Glycobiology
173
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.

174

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

175
R
R
R
Type A
Type B
Type O
176

• 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.

177

• 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.

N-acetylneuraminic acid
Oseltamivir (Tamiflu) - prodrug
178
N-acetylgalactosamine
N-acetylneuraminic acid
Fig. 23.14 Diagram of a cell-surface
glycoprotein, showing the disaccharide unit that
is recognized by an invading influenza virus.