Modified Chapter 25 Carbohydrates

1
ModifiedChapter 25Carbohydrates
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25.1Classification of Carbohydrates
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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)
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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

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Table 25.1 Some Classes of Carbohydrates

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

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25.2Fischer Projections and D-L Notation
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Fischer Projections
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Fischer Projections
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Fischer Projections of Enantiomers
12
Enantiomers of Glyceraldehyde
()-Glyceraldehyde
()-Glyceraldehyde
13
25.3The Aldotetroses
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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
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The Four Aldotetroses

• D-Erythrose and D-threose are diastereomers

D-Erythrose
D-Threose
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The Four Aldotetroses

• L-Erythrose and D-threose are diastereomers

L-Erythrose
D-Threose
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The Four Aldotetroses

• D-Threose and L-threose are enantiomers

L-Threose
D-Threose
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The Four Aldotetroses
H
D-Erythrose
L-Erythrose
D-Threose
L-Threose
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25.4Aldopentoses and Aldohexoses
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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.

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The Four D-Aldopentoses
D-Ribose
D-Arabinose
D-Xylose
D-Lyxose
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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 25.5.

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25.5A Mnemonic for Carbohydrate Configurations
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The Eight D-Aldohexoses
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The Eight D-Aldohexoses

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

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The Eight D-Aldohexoses

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

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The Eight D-Aldohexoses

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

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The Eight D-Aldohexoses

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

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The Eight D-Aldohexoses

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

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The Eight D-Aldohexoses

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

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The Eight D-Aldohexoses

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

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The Eight D-Aldohexoses

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

HO
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The Eight D-Aldohexoses

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

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The Eight D-Aldohexoses

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

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The Eight D-Aldohexoses

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

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The Eight D-Aldohexoses

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

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The Eight D-Aldohexoses

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

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The Eight D-Aldohexoses

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

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The Eight D-Aldohexoses

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

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The Eight D-Aldohexoses

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

HO
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The Eight D-Aldohexoses

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

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The Eight D-Aldohexoses

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

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The Eight D-Aldohexoses

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

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The Eight D-Aldohexoses

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

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The Eight D-Aldohexoses

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

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The Eight D-Aldohexoses

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

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The Eight D-Aldohexoses

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

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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
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25.6Cyclic Forms of CarbohydratesFuranose Forms
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Recall from Section 17.8

R"OH

• Product is a hemiacetal.

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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.

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Carbohydrates Form Cyclic Hemiacetals
1
2
3
4

• equilibrium lies far to the right
• cyclic hemiacetals that have 5-membered ringsare
  called furanose forms

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

• stereochemistry is maintained during
  cyclichemiacetal formation

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D-Erythrose
1
2
3
4
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D-Erythrose

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

1
4
2
3
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D-Erythrose
1
1
4
4
2
2
3
3
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D-Erythrose

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

1
4
2
3
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D-Erythrose
1
1
4
4
2
2
3
3
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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

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D-Erythrose
?-D-Erythrofuranose
?-D-Erythrofuranose
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D-Ribose

• furanose ring formation involves OH group at C-4

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D-Ribose

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

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D-Ribose
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D-Ribose
?-D-Ribofuranose

• CH2OH group becomes a substituent on ring

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25.7Cyclic Forms of CarbohydratesPyranose Forms
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Carbohydrates Form Cyclic Hemiacetals
5
OH
O
1
4
H
2
3

• cyclic hemiacetals that have 6-membered ringsare
  called pyranose forms

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D-Ribose
OH
H
H
OH
H
OH

• pyranose ring formation involves OH group at C-5

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D-Ribose
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D-Ribose
?-D-Ribopyranose
?-D-Ribopyranose
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D-Glucose

• pyranose ring formation involves OH group at C-5

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D-Glucose

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

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D-Glucose
?-D-Glucopyranose
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D-Glucose
?-D-Glucopyranose
?-D-Glucopyranose
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D-Glucose
?-D-Glucopyranose

• pyranose forms of carbohydrates adopt chair
  conformations

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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

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

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

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Figure 25.5

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

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Figure 25.5

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

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Figure 25.5

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

?-D-Ribofuranose (18)
?-D-Ribofuranose (6)
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25.8Mutarotation
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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.

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

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25.9Ketoses
87
Ketoses

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

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Examples
D-Ribulose
L-Xyulose
D-Fructose
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25.13Glycosides
90
Glycosides

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

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Example
D-Glucose

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

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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 and
  N-glycosides.

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Example

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

D-Ribose
Adenosine
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Example
D-Glucose

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

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Glycosides

• O-Glycosides are mixed acetals.

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O-Glycosides are mixed acetals
hemiacetal
97
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.
• Only the anomeric OH group is replaced.
• An equilibrium is established between the ? and
  ?-glycosides (thermodynamic control). The more
  stable stereoisomer predominates.

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

Methyl?-D-glucopyranoside(major product)
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Mechanism of Glycoside Formation
HCl

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

101
Mechanism of Glycoside Formation

102
Mechanism of Glycoside Formation


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25.14Disaccharides
104
Disaccharides

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

105
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)

106
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).

107
Maltose and Cellobiose
Cellobiose
Maltose
108
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.

109
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.

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25.18Reduction of Carbohydrates
111
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.

112
Reduction of D-Galactose
reducing agent NaBH4, H2O(catalytic
hydrogenation can also be used)
113
25.19Oxidation of Carbohydrates
114
Benedict's Reagent


2Cu2

Cu2O

5HO
3H2O

• Benedict's reagent is a solution of the citrate
  complex of CuSO4 in water. It is used as a test
  for "reducing sugars." Cu2 is a weak oxidizing
  agent.
• A reducing sugar is one which has an aldehyde
  function, or is in equilibrium with one that
  does.
• A positive test is the formation of a red
  precipitate of Cu2O.

115
Examples of Reducing Sugars

• Aldoses because they have an aldehyde function
  in their open-chain form.
• Ketoses because enolization establishes an
  equilibrium with an aldose.

oxidized by Cu2
116
Examples of Reducing Sugars

• Disaccharides that have a free hemiacetal
  function.

117
Examples of Reducing Sugars

• Disaccharides that have a free hemiacetal
  function.

Maltose
oxidized by Cu2
118
Glycosides are not reducing sugars
Methyl ?-D-glucopyranoside lacks a
freehemiacetal function cannot be in
equilibriumwith a species having an aldehyde
function
119
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.

120
Oxidation of D-Xylose
D-Xylose
121
Oxidation of D-Xylose

D-Xylonic acid (90)
122
Ruff Degradation Part 1,Oxidation of D-Glucose
D-Glucose
123
Ruff Degradation Part 2,Oxidized Carbon Removed
HO
D-Arabinose
124
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.

125
Nitric Acid Oxidation
HNO3
60C
D-Glucose
126
25.20Cyanohydrin Formation and Carbohydrate
Chain ExtensionKiliani-Fischer Synthesis
127
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.

128
Extending the Carbohydrate Chain

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

129
Extending the Carbohydrate Chain
separate

L-Mannononitrile
L-Gluconononitrile
130
Extending the Carbohydrate Chain
L-Mannononitrile
131
Likewise...
L-Gluconononitrile
132
25.21Epimerization and Isomerization of
Carbohydrates
133
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.

134
Epimerization
D-Mannose
D-Glucose
This equilibration can be catalyzed by hydroxide
ion.
135
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).

136
Isomerization
Enediol
137
25.22Acylation and Alkylation of Hydroxyl Groups
in Carbohydrates
138
Reactivity of Hydroxyl Groups in Carbohydrates
Hydroxyl groups in carbohydrates undergo
reactions typical of alcohols.

• acylationalkylation

139
Example Acylation of ?-D-glucopyranose
O
O
CH3COCCH3
5

140
Example Alkylation of methyl ?-D-glucopyranoside
4CH3I

141
Classical Method for Ring Size
Ring sizes (furanose or pyranose) have been
determined using alkylation as a key step.
142
Classical Method for Ring Size
Ring sizes (furanose or pyranose) have been
determined using alkylation as a key step.
H2O
H
(mixture of ? ?)
143
Classical Method for Ring Size
Ring sizes (furanose or pyranose) have been
determined using alkylation as a key step.
(mixture of ? ?)
144
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.
145
End of Chapter 25