Transcript Organic Chemistry Fifth Edition

Chapter 23
Carbohydrates
23.1
Classification of Carbohydrates
Classification of Carbohydrates
Monosaccharide
Disaccharide
Oligosaccharide
Polysaccharide
Monosaccharide
Is not cleaved to a simpler carbohydrate on
hydrolysis.
Glucose, for example, is a monosaccharide.
Disaccharide
Is cleaved to two monosaccharides on hydrolysis.
These two monosaccharides may be the
same or different.
C12H22O11 + H2O
sucrose
(a disaccharide)
C6H12O6 + C6H12O6
glucose
(a monosaccharide)
fructose
(a monosaccharide)
Higher Saccharides
Oligosaccharide:
Gives two or more monosaccharide units on
hydrolysis.
Is homogeneous—all 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.
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
23.2
Fischer Projections and D,L Notation
Fischer Projections
Fischer Projections
Fischer Projections of Enantiomers
Enantiomers of Glyceraldehyde
CH
H
D
O
OH
CH2OH
(+)-Glyceraldehyde
CH
HO
L
O
H
CH2OH
(–)-Glyceraldehyde
23.3
The Aldotetroses
An Aldotetrose
1
H
H
D
CH
2
3
4
O
OH
OH
CH2OH
Stereochemistry assigned on basis of whether
configuration of highest-numbered stereogenic center
is analogous to D or L-glyceraldehyde.
An Aldotetrose
1
H
H
CH
2
3
4
O
OH
OH
CH2OH
D-Erythrose
The Four Aldotetroses
CH
O
CH
O
H
OH HO
H
D-Erythrose and
L-erythrose are
H
OH HO
H
enantiomers.
CH2OH
D-Erythrose
CH2OH
L-Erythrose
The Four Aldotetroses
CH
O
CH
H
OH
HO
H
OH
H
CH2OH
D-Erythrose
O
H
OH
CH2OH
D-Threose
D-Erythrose and
D-threose are
diastereomers.
The Four Aldotetroses
CH
HO
O
H
CH
HO
O
H
L-Erythrose and
D-threose are
diastereomers.
HO
H
CH2OH
L-Erythrose
H
OH
CH2OH
D-Threose
The Four Aldotetroses
CH
D-Threose and
L-threose are
enantiomers.
HO
H
O
H
OH
CH2OH
D-Threose
CH
O
H
OH
HO
H
CH2OH
L-Threose
The Four Aldotetroses
CH
O
CH
O
CH
O
CH
H
OH HO
H HO
H
H
OH HO
H
OH HO
CH2OH
D-Erythrose
CH2OH
L-Erythrose
H
CH2OH
D-Threose
H
O
OH
H
CH2OH
L-Threose
23.4
Aldopentoses 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
CH
O
CH
O
CH
O
H
OH HO
H
H
OH
H
OH HO
H
H
OH
H
OH
OH
CH2OH
D-Ribose
CH2OH
D-Arabinose
H
H
CH
O
OH HO
H
HO
H
CH2OH
D-Xylose
H
OH
CH2OH
D-Lyxose
Aldohexoses
There are 16 aldopentoses.
8 belong to the D-series; 8 belong to the Lseries.
Their names and configurations are best
remembered with the aid of the mnemonic
described in Section 23.5.
23.5
A Mnemonic for Carbohydrate
Configurations
The Eight D-Aldohexoses
CH
H
O
OH
CH2OH
The Eight D-Aldohexoses
All
CH
Altruists
O
Gladly
Make
Gum
In
Gallon
Tanks
H
OH
CH2OH
The Eight D-Aldohexoses
All
Allose
Altruists
Altrose
Gladly
Glucose
Make
Mannose
Gum
Gulose
In
Idose
Gallon
Galactose
Tanks
Talose
CH
H
O
OH
CH2OH
The Eight D-Aldohexoses
Allose
CH
Altrose
O
Glucose
Mannose
Gulose
Idose
Galactose
Talose
H
OH
CH2OH
The Eight D-Aldohexoses
Allose
CH
Altrose
O
Glucose
Mannose
Gulose
H
OH
Idose
H
OH
Galactose
Talose
CH2OH
The Eight D-Aldohexoses
Allose
CH
Altrose
O
Glucose
Mannose
Gulose
Idose
Galactose
Talose
HO
H
H
OH
CH2OH
The Eight D-Aldohexoses
Allose
CH
Altrose
O
Glucose
Mannose
Gulose
H
OH
Idose
H
OH
Galactose
Talose
CH2OH
The Eight D-Aldohexoses
Allose
CH
Altrose
O
Glucose
Mannose
H
OH
Gulose
H
OH
Idose
H
OH
Galactose
Talose
CH2OH
The Eight D-Aldohexoses
Allose
CH
Altrose
O
Glucose
Mannose
HO
H
Gulose
H
OH
Idose
H
OH
Galactose
Talose
CH2OH
The Eight D-Aldohexoses
Allose
CH
Altrose
O
Glucose
Mannose
Gulose
Idose
Galactose
Talose
HO
H
H
OH
CH2OH
The Eight D-Aldohexoses
Allose
CH
Altrose
O
Glucose
Mannose
Gulose
Idose
Galactose
Talose
H
HO
OH
H
H
OH
CH2OH
The Eight D-Aldohexoses
Allose
CH
Altrose
O
Glucose
Mannose
HO
H
Gulose
HO
H
H
OH
Idose
Galactose
Talose
CH2OH
The Eight D-Aldohexoses
Allose
CH
Altrose
O
Glucose
Mannose
H
OH
Gulose
H
OH
Idose
H
OH
Galactose
Talose
CH2OH
The Eight D-Aldohexoses
Allose
CH
Altrose
O
Glucose
H
OH
Mannose
H
OH
Gulose
H
OH
Idose
H
OH
Galactose
Talose
CH2OH
The Eight D-Aldohexoses
Allose
CH
Altrose
O
Glucose
HO
H
Mannose
H
OH
Gulose
H
OH
Idose
H
OH
Galactose
Talose
CH2OH
The Eight D-Aldohexoses
Allose
CH
Altrose
O
Glucose
Mannose
HO
H
Gulose
H
OH
Idose
H
OH
Galactose
Talose
CH2OH
The Eight D-Aldohexoses
Allose
CH
Altrose
Glucose
H
Mannose
HO
O
OH
H
Gulose
H
OH
Idose
H
OH
Galactose
Talose
CH2OH
The Eight D-Aldohexoses
Allose
CH
Altrose
O
Glucose
HO
H
Mannose
HO
H
Gulose
H
OH
Idose
H
OH
Galactose
Talose
CH2OH
The Eight D-Aldohexoses
Allose
CH
Altrose
O
Glucose
Mannose
Gulose
Idose
Galactose
Talose
H
HO
OH
H
H
OH
CH2OH
The Eight D-Aldohexoses
Allose
CH
Altrose
O
Glucose
H
OH
Mannose
H
HO
OH
H
H
OH
Gulose
Idose
Galactose
Talose
CH2OH
The Eight D-Aldohexoses
Allose
CH
Altrose
O
Glucose
HO
H
Mannose
H
HO
OH
H
H
OH
Gulose
Idose
Galactose
Talose
CH2OH
The Eight D-Aldohexoses
Allose
CH
Altrose
O
Glucose
Mannose
HO
H
Gulose
HO
H
H
OH
Idose
Galactose
Talose
CH2OH
The Eight D-Aldohexoses
Allose
CH
Altrose
O
Glucose
H
OH
Mannose
HO
H
Gulose
HO
H
H
OH
Idose
Galactose
Talose
CH2OH
The Eight D-Aldohexoses
Allose
CH
Altrose
O
Glucose
HO
H
Mannose
HO
H
Gulose
HO
H
H
OH
Idose
Galactose
Talose
CH2OH
L-Aldohexoses
There are 8
aldohexoses of
H
the L-series.
They have the
HO
same name as
H
their mirror image
except the prefix is H
L- rather than D-.
CH
O
OH
H
CH
HO
H
O
H
OH
OH
HO
H
OH
HO
H
CH2OH
D-(+)-Glucose
CH2OH
L-(–)-Glucose
23.6
Cyclic Forms of Carbohydrates:
Furanose Forms
Recall from Section 17.8
R
R
C
O •• + R"OH
••
R'
••
R"O
••
C
R'
Product is a hemiacetal.
••
O
••
H
Cyclic Hemiacetals
R
R
C
O
OH
C
OH
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.
Carbohydrates Form Cyclic Hemiacetals
1
CH
O
2
OH
O
4
1
3
3
4
2
H
CH2OH
Equilibrium lies far to the right.
Cyclic hemiacetals that have 5-membered rings
are called furanose forms.
D-Erythrose
1
H
CH
2
O
OH
HH
O
4
H
3
4
OH
CH2OH
H
H
1
3
OH
OH
2
OH
Stereochemistry is maintained during cyclic
hemiacetal formation.
H
D-Erythrose
1
2
3
4
1
4
turn 90°
3
2
D-Erythrose
Move O into
position by rotating
about bond
between carbon-3
and carbon-4.
1
4
3
2
D-Erythrose
1
4
3
2
1
4
3
2
D-Erythrose
1
4
3
2
Close ring by
hemiacetal formation
between OH at C-4
and carbonyl group.
D-Erythrose
1
4
3
2
1
4
3
2
D-Erythrose
1
H
CH
2
anomeric carbon
O
OH
HH
O
4
H
3
4
OH
CH2OH
H
3
OH
H
OH
1
2
H
OH
Stereochemistry is variable at anomeric carbon;
two diastereomers are formed.
D-Erythrose
HH
O
4
H
3
OH
H
H
1
2
OH
OH
-D-Erythrofuranose
HH
O
4
H
3
OH
H
OH
1
2
H
OH
-D-Erythrofuranose
D-Ribose
1
H
CH
O
2
OH
H
3
OH
H
4
OH
5 CH
2OH
Furanose ring formation involves OH group at C-4.
D-Ribose
1
H
CH
O
5
2
OH
H
H
3
OH
4
H
4
OH
HO 3
5 CH
2OH
CH2OH 1
H
H
CH
2
OH
OH
Need C(3)-C(4) bond rotation to put OH in proper
orientation to close 5-membered ring.
O
D-Ribose
5
5
HOCH2 OH
H
4
H
3
OH
H
2
OH
H
1
CH
O
4
CH2OH 1
H
H
CH
HO 3
2
OH
OH
O
D-Ribose
5
5
HOCH2 OH
H
4
H
3
OH
H
2
OH
1
CH
O
HOCH2
H
O H
4
H
3
OH
2
OH
1
H
OH
-D-Ribofuranose
CH2OH group becomes a substituent on ring.
23.7
Cyclic Forms of Carbohydrates:
Pyranose Forms
Carbohydrates Form Cyclic Hemiacetals
1
CH
O
5
2
3
4
5
OH
O
1
4
3
2
H
CH2OH
Cyclic hemiacetals that have 6-membered rings
are called pyranose forms.
D-Ribose
1
H
CH
O
5
2
OH
H
H
3
OH
4
H
4
OH
HO 3
5 CH
2OH
CH2OH
H
H
1
CH
O
2
OH
OH
Pyranose ring formation involves OH group at C-5.
D-Ribose
H
H
4
HO
5
H
H
3
OH
5
O
OH
H
1
2
H
OH
-D-Ribopyranose
H
4
CH2OH
H
H
HO 3
2
OH
OH
1
CH
O
D-Ribose
H
H
4
HO
5
H
H
3
OH
H
O
OH
H
1
2
H
OH
-D-Ribopyranose
H
4
HO
5
H
H
3
OH
O
H
1
H
2
OH
OH
-D-Ribopyranose
D-Glucose
1
CH
O
2
OH
HO
3
H
H
4
H
H
5
6
OH
OH
6
H
CH2OH
5
H
OH
4
OH
H
HO 3
CH
1
2
H
OH
CH2OH
Pyranose ring formation involves OH group at C-5.
O
D-Glucose
6
6
HOCH2 OH
H 5
H
4
OH
H
HO 3
CH
1
2
H
OH
O
H
CH2OH
5
H
OH
4
OH
H
HO 3
CH
1
2
H
OH
Need C(4)-C(5) bond rotation to put OH in proper
orientation to close 6-membered ring.
O
D-Glucose
6
6
HOCH2
HOCH2 OH
H 5
H
4
OH
H
HO
3
H
CH
1
2
H
O
4
OH
HO
5
H
OH
3
H
O
OH
H
1
2
H
OH
-D-Glucopyranose
D-Glucose
6
6
HOCH2
HOCH2
H
4
HO
5
H
OH
3
H
O
H
2
H
H
1
4
OH
HO
OH
-D-Glucopyranose
5
H
OH
3
H
O
OH
H
1
2
H
OH
-D-Glucopyranose
D-Glucose
6
HOCH2
H
4
HO
5
H
OH
3
H
O
OH
H
1
2
H
OH
-D-Glucopyranose
Pyranose forms of carbohydrates adopt chair
conformations.
D-Glucose
6
HOCH2
H 6
HOCH2 H
4
HO
HO
H
O
5
4
OH
2
3
H
H
1
OH
H
HO
5
H
OH
3
H
O
OH
H
1
2
H
OH
-D-Glucopyranose
All substituents are equatorial in -D-glucopyranose.
D-Glucose
H
HOCH2 H
H
HOCH2 H
O
HO
HO
OH
O
HO
HO
H
1
H
H
1
OH
H
H
-D-Glucopyranose
OH
H
OH
-D-Glucopyranose
OH group at anomeric carbon is axial
in -D-glucopyranose.
D-Ribose
1
H
CH
O
2
OH
H
3
OH
H
4
OH
5 CH
2OH
Less than 1% of the open-chain form of D-ribose
is present at equilibrium in aqueous solution.
D-Ribose
76% of the D-ribose is a mixture of the  and pyranose forms, with the -form predominating.
H
H
H
H
O
HO
H
O
HO
H
OH
H
H
H
1
H
OH
OH
H
-D-Ribopyranose (56%)
H
OH
OH
OH
-D-Ribopyranose (20%)
D-Ribose
The  and -furanose forms comprise 24% of
the mixture.
HOCH2
H
O H
OH
H
H
OH
OH
-D-Ribofuranose (18%)
HOCH2
H
O H
H
OH
H
OH
OH
-D-Ribofuranose (6%)
23.8
Mutarotation
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
H
HOCH2 H
H
HOCH2 H
O
HO
HO
OH
O
HO
HO
H
1
H
H
1
OH
H
H
-D-Glucopyranose
Initial: []D +18.7°
H
OH
OH
-D-Glucopyranose
Initial: []D +112.2°
Final: []D +52.5°
Mutarotation of D-Glucose
H
HOCH2 H
H
HOCH2 H
O
HO
HO
OH
O
HO
HO
H
1
H
H
1
OH
H
H
-D-Glucopyranose
H
OH
OH
-D-Glucopyranose
Explanation: After being dissolved in water, the
 and  forms slowly interconvert via the openchain form. An equilibrium state is reached that
contains 64%  and 36% .
23.9
Carbohydrate 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.
2%
98%
Origin of the Anomeric Effect is not well
understood
Fig. 23.6
23.10
Ketoses
Ketoses
Ketoses are carbohydrates that have a ketone
carbonyl group in their open-chain form.
C-2 is usually the carbonyl carbon.
Examples
CH2OH
CH2OH
CH2OH
O
O
O
H
OH
H
H
OH
HO
CH2OH
OH
H
CH2OH
HO
H
H
OH
H
OH
CH2OH
D-Ribulose
L-Xylulose
D-Fructose
23.11
Deoxy Sugars
Deoxy Sugars
Often one or more of the carbons of a
carbohydrate will lack an oxygen substituent.
Such compounds are called deoxy sugars.
Examples
CH
O
CH
O
H
H
H
OH
H
OH
H
OH
H
OH
HO
H
CH2OH
HO
H
CH3
2-Deoxy-D-ribose
6-Deoxy-L-mannose
23.12
Amino Sugars
Amino Sugars
An amino sugar has one or more of its oxygens
replaced by nitrogen.
Example
HOCH2
O
HO
HO
OH
NH
O
C
CH3
N-Acetyl-D-glucosamine
Example
OH
H3C
HO
O
NH2
L-Daunosamine
23.13
Branched-Chain Carbohydrates
Branched-Chain Carbohydrates
Carbohydrates that don't have a continuous
chain of carbon-carbon bonds are called
branched-chain carbohydrates.
Examples
CH
H
HO
O
OH
CH3
H3C
CH2OH
CH2OH
D-Apiose
HO
OH
O
NH2
L-Vancosamine
23.14
Glycosides: The Fischer
Glycosidation
Glycosides
Glycosides have a substituent other than OH at
the anomeric carbon.
Usually the atom connected to the anomeric
carbon is oxygen.
Example
HOCH2
O
HO
HO
OH
OH
D-Glucose
Linamarin is
an O-glycoside
derived from
D-glucose.
HOCH2
HO
HO
O
CH3
OCC
OH
CH3
N
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 Nglycoside derived from
D-ribose
NH2
N
HOCH2
H O
H
OH
OH
H
H
OH
D-Ribose
N
N
HOCH2 N
H O H
H
OH
H
OH
Adenosine
Example
HOCH2
O
HO
HO
OH
OH
D-Glucose
Sinigrin is an
HOCH2
S-glycoside HO
derived from
HO
D-glucose.
O
NOSO3K
SCCH2CH
OH
CH2
Glycosides
O-Glycosides are mixed acetals.
O-Glycosides are mixed acetals
CH
O
O
OH
hemiacetal
H
CH2OH
ROH
O
OR
H
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
1
CH
O
2
OH
HO
3
H
H
4
H
H
5
6
OH
OH
CH2OH
D-Glucose
HOCH2
HO
HO
CH3OH
O
OCH3
OH
HCl
+
HOCH2
HO
HO
O
OH
OCH3
Preparation of Glycosides
HOCH2
Methyl
-D-glucopyranoside
HO
HO
O
OCH3
OH
+
HOCH2
Methyl
HO
-D-glucopyranoside
HO
(major product)
(attributed to the anomeric
effect)
O
OH
OCH3
Mechanism of Glycoside Formation
HOCH2
HO
HO
•• •
O•
OH
OH
HCl
HOCH2
HO
HO
••
O ••
Carbocation is stabilized
by lone-pair donation from
+
oxygen of the ring.
H
OH
Mechanism of Glycoside Formation
HOCH2
•• •
O•
HO
HO
OH
HOCH2
HO
HO
CH3
HOCH2
O
HO
O •• + HO
+
H
OH +
O
H3C •• H
CH3
••
•• O ••
O ••
H
+
OH
H
Mechanism of Glycoside Formation
HOCH2
HO
HO
•• •
O•
OH
HOCH2
HO
HO
CH3
HOCH2
O
HO
O •• + HO
+
H
+
–H
OH +
O
H3C •• H
HOCH2
••
O ••
OH
HO
HO
••
OCH3 +
••
••
O ••
OH
•• OCH
3
••
23.15
Disaccharides
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
HOCH2
HOCH2
O
HO
1
HO

OH
O
O
OH
4
HO
Maltose
OH
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)
Maltose and Cellobiose
HOCH2
HOCH2
O
HO
1
HO

OH
O
O
OH
4
HO
Cellobiose
OH
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).
Maltose and Cellobiose
Maltose
Cellobiose
Cellobiose and Lactose
HOCH2
HOCH2
O
HO
1
HO

OH
O
O
OH
4
HO
Cellobiose
OH
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.
Cellobiose and Lactose
HOCH2
HOCH2
O
HO
1
HO

OH
O
O
OH
4
HO
Lactose
OH
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.
23.16
Polysaccharides
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.
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 (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.
23.17
Reactions 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.
23.18
Reduction 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
Reducing agent: NaBH4, H2O
(catalytic hydrogenation can also be used)
CH
CH2OH
O
-D-galactofuranose
-D-galactofuranose
-D-galactopyranose
-D-galactopyranose
H
OH
H
OH
HO
H
HO
H
HO
H
HO
H
H
OH
CH2OH
H
OH
CH2OH
D-Galactitol (90%)
23.19
Oxidation of Monosaccharides
Oxidation Occurs at the Ends
Easiest to oxidize the aldehyde and the primary
alcohol functions.
CH
O
CH2OH
Aldose
CO2H
CH
CH2OH
CO2H
Aldonic acid
O
Uronic acid
CO2H
CO2H
Aldaric acid
Oxidation of Reducing Sugars
The compounds formed on oxidation of
reducing sugars are called aldonic acids.
Aldonic acids exist as lactones when 5- or 6membered rings can form.
A standard method for preparing aldonic acids
uses Br2 as the oxidizing agent.
Oxidation of D-Xylose
CH
H
HO
H
O
OH
H
OH
CH2OH
D-Xylose
CO2H
Br2
H2O
H
HO
H
OH
H
OH
CH2OH
D-Xylonic acid (90%)
Oxidation of D-Xylose
O
HO
HO
OH
CO2H
O
H
HO
+
H
HOCH2
OH O
O
OH
OH
H
OH
CH2OH
D-Xylonic acid (90%)
Uronic Acids
Uronic acids contain both an aldehyde and a
terminal CO2H function.
CH
H
O
OH
HO
H
H
OH
H
OH
HO2C
HO
HO
O
OH
OH
CO2H
D-Glucuronic acid
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
CH
H
O
CO2H
OH
HO
H
H
OH
H
OH
CH2OH
D-Glucose
HNO3
60°C
H
OH
HO
H
H
OH
H
OH
CO2H
D-Glucaric acid (41%)
23.20
Periodic Acid Oxidation
Recall Periodic Acid Oxidation
Section 15.11: Vicinal diols are cleaved by HIO4.
C
HO
HIO4
C
C
O + O
OH
Cleavage of a vicinal diol consumes 1 mol of
HIO4.
C
Also Cleaved by HIO4
-Hydroxy carbonyl compounds
R
O
RC
HIO4
C
OH
C
O + O
C
HO
Cleavage of an -hydroxy carbonyl compound
consumes 1 mol of HIO4. One of the products is
a carboxylic acid.
Also Cleaved by HIO4
R2C
HO
Compounds that contain three contiguous
carbons bearing OH groups:
O
CH CR'2
HIO4
R2C O + HCOH
OH OH
+ R'2C
O
2 mol of HIO4 are consumed. 1 mole of formic
acid is produced.
Structure Determination Using HIO4
Distinguish between furanose and pyranose forms
of methyl arabinoside:
HOCH2
O
HO
OH
OCH3
2 vicinal OH groups;
consumes 1 mol of HIO4
OH
O
HO
HO
OCH3
3 vicinal OH groups;
consumes 2 mol of HIO4
23.21
Cyanohydrin Formation and
Chain 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.
Extending the Carbohydrate Chain
CN
CH
-L-arabinofuranose
O
CHOH
-L-arabinofuranose
H
-L-arabinopyranose
HO
H
HO
H
-L-arabinopyranose
HO
H
HO
H
OH HCN
CH2OH
H
OH
CH2OH
The cyanohydrin is a mixture of two stereoisomers that
differ in configuration at C-2; these two diastereomers are
separated in the next step.
Extending the Carbohydrate Chain
H
H
CN
CN
CN
HO
OH
OH
+
H
CHOH
H
OH
separate
H
OH
HO
H
HO
H
HO
H
HO
H
HO
H
HO
H
CH2OH
L-Mannononitrile
CH2OH
L-Gluconononitrile
CH2OH
Extending the Carbohydrate Chain
CN
CH
H
OH
H
OH
HO
H
HO
H
CH2OH
L-Mannononitrile
H2, H2O
Pd, BaSO4
O
H
OH
H
OH
HO
H
HO
H
CH2OH
L-Mannose
(56% from L-arabinose)
Likewise...
CN
HO
H
CH
H
OH
HO
H
HO
H
CH2OH
L-Gluconononitrile
HO
H2, H2O
Pd, BaSO4
H
O
H
OH
HO
H
HO
H
CH2OH
L-Glucose
(26% from L-arabinose)
23.22
Epimerization, Isomerization,
and 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
CH
CHOH
O
H
OH
HO
H
H
H
O
OH
HO
H
HO
H
HO
H
OH
H
OH
H
OH
OH
H
OH
H
OH
CH2OH
D-Glucose
C
CH
CH2OH
Enediol
CH2OH
D-Mannose
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
CH
O
CHOH
CHOH
CH2OH
C
C
OH
O
HO
H
HO
H
HO
H
H
OH
H
OH
H
OH
H
OH
H
OH
H
OH
CH2OH
D-Glucose or
D-Mannose
CH2OH
Enediol
CH2OH
D-Fructose
Retro-Aldol Cleavage
When D-glucose 6-phosphate undergoes the
reaction shown on the preceding slide, the Dfructose that results is formed as its 1,6diphosphate.
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
CH2OP(O)(OH)2
CH2OP(O)(OH)2
C
C
O
HO
H
H
OH
H
OH
aldolase
CH2OP(O)(OH)2
D-Fructose
1,6-phosphate
O
CH2OH
CH
H
O
OH
CH2OP(O)(OH)2
23.23
Acylation and Alkylation of
Carbohydrate Hydroxyl Groups
Reactivity of Hydroxyl Groups in
Carbohydrates
Hydroxyl groups in carbohydrates undergo
reactions typical of alcohols.
acylation
alkylation
Example: Acylation of -D-Glucopyranose
O O
HOCH2
O
HO
HO
5 CH3COCCH3
+
OH
OH
pyridine
O
O
CH3COCH2
O
CH3CO
CH3CO
O
(88%)
CH3CO
O
OCCH3
O
Example: Alkylation of Methyl -D-Glucopyranoside
HOCH2
HO
HO
O
4CH3I
+
OH
OCH3
Ag2O, CH3OH
CH3OCH2
CH3O
CH3O
O
(97%)
CH3O
OCH3
Classical Method for Ring Size
Ring sizes (furanose or pyranose) have been
determined using alkylation as a key step.
CH3OCH2
HOCH2
HO
HO
O
CH3O
CH3O
O
CH3O
OH
OCH3
OCH3
Classical Method for Ring Size
Ring sizes (furanose or pyranose) have been
determined using alkylation as a key step.
CH3OCH2
CH3O
CH3O
CH3OCH2
O
CH3O
H2O
H+
OH
(mixture of  + )
CH3O
CH3O
O
CH3O
OCH3
Classical Method for Ring Size
Ring sizes (furanose or pyranose) have been
determined using alkylation as a key step.
CH
H
CH3OCH2
CH3O
CH3O
CH3O
O
CH3O
OH
(mixture of  + )
O
OCH3
H
H
OCH3
H
OH
CH2OCH3
Classical Method for Ring Size
Ring sizes (furanose or pyranose) have been
determined using alkylation as a key step.
CH
H
This carbon has OH
instead of OCH3.
Therefore, its O was the
oxygen in the ring.
CH3O
O
OCH3
H
H
OCH3
H
OH
CH2OCH3
23.24
Glycosides: Synthesis of
Oligosaccharides
Disaccharides
When two carbohydrates combine, both
constitutionally isomeric and stereoisomeric
pyranosides are possible.
Gentiobiose is a -(16) glycoside of two
pyranosyl forms of D-glucose:

1
6
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
For the synthesis of gentiobiose:
Glycosyl donor
Glycosyl acceptor
AgOSO2CF3
collidine, toluene
Stereoselective for -disaccharide, (Mech. 23.3)
23.25
Glycobiology
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.
R
Type A
R
Type B
R
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 Nacetylneuraminic acid before the virus can
adhere to and infect a new cell.
N-acetylneuraminic acid
Oseltamivir (Tamiflu) - prodrug
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.