Chapter 23 Carbohydrates
description
Transcript of 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
Fischer Projections of Enantiomers
Enantiomers of Glyceraldehyde
CH O
CH2OH
H OHD
CH O
CH2OH
HHOL
(+)-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
CH O
CH2OH
H OH
H OH
1
2
3
4D
An Aldotetrose
1
2
3
4
D-Erythrose
CH O
CH2OH
H OH
H OH
The Four Aldotetroses
D-Erythrose L-Erythrose
D-Erythrose and L-erythrose are enantiomers.
CH O
CH2OH
H OH
H OH
CH O
CH2OH
HO H
HO H
The Four Aldotetroses
CH O
CH2OH
HHO
H OH
D-Erythrose D-Threose
D-Erythrose and D-threose are diastereomers.
CH O
CH2OH
H OH
H OH
The Four Aldotetroses
L-Erythrose D-Threose
L-Erythrose and D-threose are diastereomers.
CH O
CH2OH
HHO
H OH
CH O
CH2OH
HHO
HO H
The Four Aldotetroses
D-Threose
D-Threose and L-threose are enantiomers.
L-Threose
CH O
CH2OH
HHO
H OH
CH O
CH2OH
OHH
HHO
The Four Aldotetroses
D-Erythrose L-Erythrose D-Threose L-Threose
CH O
CH2OH
H OH
H OH
CH O
CH2OH
HHO
HO H
CH O
CH2OH
HHO
H OH
CH O
CH2OH
OHH
HHO
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
CH2OH
H OH H OH H OH H OH
CH O
CH2OH
CH O CH O
CH2OH
CH O
CH2OH
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
CH O
CH2OH
H OH
All
Altruists
Gladly
Make
Gum
In
Gallon
Tanks
The Eight D-Aldohexoses
CH O
CH2OH
H OH
All Allose
Altruists Altrose
Gladly Glucose
Make Mannose
Gum Gulose
In Idose
Gallon Galactose
Tanks Talose
The Eight D-Aldohexoses
CH O
CH2OH
H OH
Allose
Altrose
Glucose
Mannose
Gulose
Idose
Galactose
Talose
The Eight D-Aldohexoses
CH O
CH2OH
H OH
Allose
Altrose
Glucose
Mannose
Gulose
Idose
Galactose
Talose
The Eight D-Aldohexoses
CH O
CH2OH
H OH
OHH
Allose
Altrose
Glucose
Mannose
Gulose
Idose
Galactose
Talose
The Eight D-Aldohexoses
CH O
CH2OH
H OH
HO H
Allose
Altrose
Glucose
Mannose
Gulose
Idose
Galactose
Talose
The Eight D-Aldohexoses
CH O
CH2OH
H OH
OHH
Allose
Altrose
Glucose
Mannose
Gulose
Idose
Galactose
Talose
The Eight D-Aldohexoses
CH O
CH2OH
H OH
OHH
OHH
Allose
Altrose
Glucose
Mannose
Gulose
Idose
Galactose
Talose
The Eight D-Aldohexoses
CH O
CH2OH
H OH
OHH
HO H
Allose
Altrose
Glucose
Mannose
Gulose
Idose
Galactose
Talose
The Eight D-Aldohexoses
CH O
CH2OH
H OH
HO H
Allose
Altrose
Glucose
Mannose
Gulose
Idose
Galactose
Talose
The Eight D-Aldohexoses
CH O
CH2OH
H OH
HO H
H OH
Allose
Altrose
Glucose
Mannose
Gulose
Idose
Galactose
Talose
The Eight D-Aldohexoses
CH O
CH2OH
H OH
HO H
HHO
Allose
Altrose
Glucose
Mannose
Gulose
Idose
Galactose
Talose
The Eight D-Aldohexoses
CH O
CH2OH
H OH
OHH
OHH
Allose
Altrose
Glucose
Mannose
Gulose
Idose
Galactose
Talose
The Eight D-Aldohexoses
CH O
CH2OH
H OH
OHH
OHH
OHH
Allose
Altrose
Glucose
Mannose
Gulose
Idose
Galactose
Talose
The Eight D-Aldohexoses
CH O
CH2OH
H OH
OHH
OHH
HO H
Allose
Altrose
Glucose
Mannose
Gulose
Idose
Galactose
Talose
The Eight D-Aldohexoses
CH O
CH2OH
H OH
OHH
HO H
Allose
Altrose
Glucose
Mannose
Gulose
Idose
Galactose
Talose
The Eight D-Aldohexoses
CH O
CH2OH
H OH
OHH
HO H
OHH
Allose
Altrose
Glucose
Mannose
Gulose
Idose
Galactose
Talose
The Eight D-Aldohexoses
CH O
CH2OH
H OH
OHH
HO H
HO H
Allose
Altrose
Glucose
Mannose
Gulose
Idose
Galactose
Talose
The Eight D-Aldohexoses
CH O
CH2OH
H OH
HO H
H OH
Allose
Altrose
Glucose
Mannose
Gulose
Idose
Galactose
Talose
The Eight D-Aldohexoses
CH O
CH2OH
H OH
HO H
H OH
OHH
Allose
Altrose
Glucose
Mannose
Gulose
Idose
Galactose
Talose
The Eight D-Aldohexoses
CH O
CH2OH
H OH
HO H
H OH
HO H
Allose
Altrose
Glucose
Mannose
Gulose
Idose
Galactose
Talose
The Eight D-Aldohexoses
CH O
CH2OH
H OH
HO H
HHO
Allose
Altrose
Glucose
Mannose
Gulose
Idose
Galactose
Talose
The Eight D-Aldohexoses
CH O
CH2OH
H OH
HO H
HHO
OHH
Allose
Altrose
Glucose
Mannose
Gulose
Idose
Galactose
Talose
The Eight D-Aldohexoses
CH O
CH2OH
H OH
HO H
HHO
HO H
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
CH O
CH2OH
H
H
H
H
OH
HO
HO
HO
CH O
CH2OH
H OH
OHH
HO H
OHH
23.6
Cyclic Forms of Carbohydrates:
Furanose Forms
Recall from Section 17.8
R"OHC••O ••
R
R'
R"O C O H••
••
••
••
R
R'
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.
R
C O
OH
C
OHR
O
Equilibrium lies far to the right.
Cyclic hemiacetals that have 5-membered ringsare called furanose forms.
Carbohydrates Form Cyclic Hemiacetals
CH O
CH2OH
1
2
3
4
H
OHO
1
23
4
Stereochemistry is maintained during cyclichemiacetal formation.
D-Erythrose
CH O
CH2OH
1
2
3
4
H
OHO
1
23
4
H
H
OH
OH
H H H
OHOHH
D-Erythrose
turn 90°
1
23
4
1
2
3
4
D-Erythrose
Move O into position by rotating about bond between carbon-3 and carbon-4.
1
23
4
D-Erythrose
1
23
41
23
4
D-Erythrose
1
23
4Close ring by hemiacetal formation between OH at C-4 and carbonyl group.
D-Erythrose
1
23
41
23
4
Stereochemistry is variable at anomeric carbon;two diastereomers are formed.
D-Erythrose
anomeric carbonCH O
CH2OH
1
2
3
4
H
OH
OH
H
H
OHO
1
23
4
H H H
OHOHH
D-Erythrose
-D-Erythrofuranose -D-Erythrofuranose
H
OHO
1
23
4
H H H
OHOHH
OH
HO
1
23
4
H H H
OHOHH
D-Ribose
CH O
CH2OH
H OH
H OH
H OH
1
2
3
4
5
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
1
23
4
5
CH O
CH2OH
H OH
H OH
H OH
1
2
3
4
5
D-Ribose CH OHH
H CH2OH
OHOHHO
1
23
4
5 CH OHH
H
HOCH2
OHOH
OH1
23
4
5
D-Ribose
CH2OH group becomes a substituent on ring.
CH OHH
H
HOCH2
OHOH
OH1
23
4
5 HOCH2
H
OHO
1
23
4
H H
OHOHH
5
-D-Ribofuranose
23.7
Cyclic Forms of Carbohydrates:
Pyranose Forms
Cyclic hemiacetals that have 6-membered ringsare called pyranose forms.
Carbohydrates Form Cyclic Hemiacetals
H
OHO1
23
4
52
3
4
CH O
CH2OH
1
5
D-Ribose CH OHH
H CH2OH
OHOHHO
1
23
4
5
Pyranose ring formation involves OH group at C-5.
CH O
CH2OH
H OH
H OH
H OH
1
2
3
4
5
D-Ribose CH OHH
H CH2OH
OHOHHO
1
23
4
5 H
OHO1
23
4
OHOHHO
HH
HH
H5
-D-Ribopyranose
D-Ribose H
OHO1
23
4
OHOHHO
HH
HH
H5
-D-Ribopyranose
OH
HO1
23
4
OHOHHO
HH
HH
H5
-D-Ribopyranose
D-Glucose
2
3
4
5
CH O
CH2OH
1
H
HO
H OH
H
OH
H OH6
OH
CH OHOH
H CH2OH
OHHHO
1
23
4
5
6
H
Pyranose ring formation involves OH group at C-5.
D-Glucose CH OHOH
H CH2OH
OHHHO
1
23
4
5
6
H
OH
CH OHOH
H
HOCH2
OHHHO
1
23
4
5
6
HOH
Need C(4)-C(5) bond rotation to put OH in proper orientation to close 6-membered ring.
D-Glucose CH OHOH
H
HOCH2
OHHHO
1
23
4
5
6
HOH
-D-Glucopyranose
H
OHO1
23
4
OHHHO
HOH
HH
HOCH2
5
6
D-Glucose
-D-Glucopyranose
H
OHO1
23
4
OHHHO
HOH
HH
HOCH2
5
6
-D-Glucopyranose
OH
HO1
23
4
OHHHO
HOH
HH
HOCH2
5
6
D-Glucose
-D-Glucopyranose
H
OHO1
23
4
OHHHO
HOH
HH
HOCH2
5
6
Pyranose forms of carbohydrates adopt chair conformations.
D-Glucose
-D-Glucopyranose
H
OHO1
23
4
OHHHO
HOH
HH
HOCH2
5
6 OH
HOH
H
HOHO
H
HH
HOCH2
O
All substituents are equatorial in -D-glucopyranose.
123
45
6
D-Glucose
-D-Glucopyranose
OH
HOH
H
HOHO
H
HH
HOCH2
O
OH group at anomeric carbon is axialin -D-glucopyranose.
1
-D-Glucopyranose
H
OHOH
H
HOHO
H
HH
HOCH2
O
1
D-Ribose
Less than 1% of the open-chain form of D-ribose is present at equilibrium in aqueous solution.
CH O
CH2OH
H OH
H OH
H OH
1
2
3
4
5
D-Ribose OH
HOH
H
HHO
H
OHH
O
-D-Ribopyranose (56%)
H
HO
-D-Ribopyranose (20%)
H
OHOH
H
H
H
OHH
O
1
H
76% of the D-ribose is a mixture of the and - pyranose forms, with the -form predominating.
D-Ribose HOCH2
H
OHOH H
OHOHH
-D-Ribofuranose (18%)
HOCH2
OH
HOH H
OHOHH
-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
OH
HOH
H
HOHO
H
HH
HOCH2
O
1
-D-Glucopyranose
H
OHOH
H
HOHO
H
HH
HOCH2
O
1
Initial: []D +18.7° Initial: []D +112.2°
Final: []D +52.5°
Mutarotation of D-Glucose
-D-Glucopyranose
OH
HOH
H
HOHO
H
HH
HOCH2
O
1
-D-Glucopyranose
H
OHOH
H
HOHO
H
HH
HOCH2
O
1
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.
O OCl
Cl
OAc
OAc
OAc
AcOAcO
OAc
98%2%
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
HO
H
CH2OH
CH2OH
O
H
OH
H
H
CH2OH
CH2OH
O
OH
OH HO
H
CH2OH
CH2OH
O
OH
H
H OH
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
CH O
CH2OH
H OH
H OH
H H
6-Deoxy-L-mannose
CH O
CH3
HO H
H OH
H OH
HO H
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
O
OH
NH
HOHO
HOCH2
C
CH3
O
Example
L-Daunosamine
O
OH
HO
H3C
NH2
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
CH O
CH2OH
H OH
HO CH2OH
D-Apiose
O
OH
HO
H3C
NH2
CH3
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.
O
OH
OH
HOHO
HOCH2 O
OCC
OH
HOHO
HOCH2 CH3
N
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
H
OHOH H
OHOHH
D-Ribose
HOCH2
H
NOH H
OHOHH
N
NH2
N
N
Adenosine
Example
Sinigrin is an S-glycoside derived from D-glucose.
O
OH
OH
HOHO
HOCH2
D-Glucose O
SCCH2CH
OH
HOHO
HOCH2
CH2
NOSO3K
Glycosides
O-Glycosides are mixed acetals.
O-Glycosides are mixed acetals H
OHO
CH O
CH2OH
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
CH3OH
HCl
D-Glucose
O
OCH3
OH
HOHO
HOCH2
+ O
OCH3
OH
HOHO
HOCH2
2
3
4
5
CH O
CH2OH
1
H
HO
H OH
H
OH
H OH6
Preparation of Glycosides O
OCH3
OH
HOHO
HOCH2
+ O
OCH3
OH
HOHO
HOCH2
Methyl-D-glucopyranoside
Methyl-D-glucopyranoside
(major product)(attributed to the anomeric
effect)
Mechanism of Glycoside Formation
HCl
Carbocation is stabilized by lone-pair donation from oxygen of the ring.
O
OH
OH
HOHO
HOCH2••
•• O
OH
HOHO
HOCH2
+
H
•• ••
Mechanism of Glycoside Formation
O
OH
HOHO
HOCH2
+
H
•• •• O••
H
CH3
••
O
O
OH
HOHO
HOCH2 •• ••CH3
H
••+
+
+
O
OH
HOHO
HOCH2
OHH3C ••
Mechanism of Glycoside Formation O
O
OH
HOHO
HOCH2 •• ••CH3
H
••+
+
O
OH
HOHO
HOCH2
OHH3C ••
+
+
••
O
OCH3
OH
HOHO
HOCH2 •• ••
••
–H+ ••
O
OCH3
OH
HOHO
HOCH2
••
••
••
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)
O
HOCH2 HOCH2
OH
OHHOOHHO
HOO O1 4
Maltose and Cellobiose
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).
O
HOCH2 HOCH2
OH
OHHOOHHO
HOO O1 4
Maltose and Cellobiose
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.
O
HOCH2 HOCH2
OH
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.
O
HOCH2 HOCH2
OH
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-galactofuranose
-D-galactopyranose
-D-galactopyranose
CH2OH
H OH
HHO
HHO
H OH
CH O
CH2OH
H OH
HHO
HHO
H OH
CH2OH
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
CO2H
CH2OH
CH O
CO2H
CO2H
CO2H
CH O
CH2OH
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
HO
H OH
H OH
H
CH O
CH2OH
Br2
H2O
D-Xylose
HO
H OH
H OH
H
CH2OH
CO2H
D-Xylonic acid (90%)
Oxidation of D-Xylose
HO
H OH
H OH
H
CH2OH
CO2H
D-Xylonic acid (90%)
OO
OH
OHHOCH2
O
O
OH
HOHO
+
Uronic Acids
CH O
CO2H
H OH
H OH
H
H OH
HO
D-Glucuronic acid
HO
HO
OH
OH
HO2CO
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
CH O
CH2OH
H OH
H OH
H
H OH
HOHNO3
60°C
CO2H
H OH
H OH
H
H OH
HO
CO2H
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.
CC
HO OH
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.
CRC
OH
HIO4C O O C+
-Hydroxy carbonyl compounds
O R
HO
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:
HCOH
OCH
OH
R2C CR'2
OHHO
+
O
HOCH2
HO
OH
OCH3
Structure Determination Using HIO4
Distinguish between furanose and pyranose formsof methyl arabinoside:
HO
HO
OOH
OCH3
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-arabinofuranose
-L-arabinopyranose
-L-arabinopyranose
CH2OH
HHO
HHO
H OH
CH O
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.
CH2OH
HO H
HHO
OHH
CN
CHOH
HCN
Extending the Carbohydrate Chain
CH2OH
HO H
HHO
OHH
CN
CHOH
+separate
L-Mannononitrile L-Gluconononitrile
CH2OH
HO H
HHO
OHH
H OH
CN
CH2OH
HO H
HHO
OHH
HO H
CN
Extending the Carbohydrate Chain
CH2OH
HO H
HHO
OHH
H OH
CN
L-Mannononitrile
H2, H2O
Pd, BaSO4
L-Mannose(56% from L-arabinose)
CH2OH
HO H
HHO
OHH
H OH
CH O
Likewise...
CH2OH
HO H
HHO
OHH
HO H
CN
L-Gluconononitrile
H2, H2O
Pd, BaSO4
L-Glucose(26% from L-arabinose)
CH2OH
HO H
HHO
OHH
HO H
CH O
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
CH O
CH2OH
H OH
H OH
H
H OH
HO
D-MannoseD-Glucose
CH O
CH2OH
H OH
H OH
H
HO H
HO
Enediol
CH2OH
H OH
H OH
H
OH
HO
CHOH
C
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
CH2OH
H OH
H OH
H
OH
HO
CHOH
C
D-Glucose orD-Mannose
CH O
CH2OH
H OH
H OH
HHO
CHOH
D-Fructose
CH2OH
CH2OH
H OH
H OH
HHO
C O
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
H OH
H OH
HHO
C O
CH2OP(O)(OH)2
aldolase
H OH
CH2OP(O)(OH)2
CH O
CH2OP(O)(OH)2
C O
CH2OH
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
OHOH
HOHO
HOCH2
+ CH3COCCH3
O O
5
pyridine O
O
CH3COCH2
O
CH3CO
O
CH3CO
OCH3CO
OOCCH3
(88%)
Example: Alkylation of Methyl -D-Glucopyranoside O
OCH3
OH
HOHO
HOCH2
+ 4CH3I
Ag2O, CH3OH O
OCH3
CH3O
CH3OCH3O
CH3OCH2
(97%)
Classical Method for Ring Size
Ring sizes (furanose or pyranose) have been determined using alkylation as a key step.
O
OCH3
OH
HOHO
HOCH2
O
OCH3
CH3O
CH3OCH3O
CH3OCH2
Classical Method for Ring Size
Ring sizes (furanose or pyranose) have been determined using alkylation as a key step.
O
OCH3
CH3O
CH3OCH3O
CH3OCH2
H2O
H+
(mixture of + )
O
OHCH3O
CH3OCH3O
CH3OCH2
Classical Method for Ring Size
Ring sizes (furanose or pyranose) have been determined using alkylation as a key step.
(mixture of + )
O
OHCH3O
CH3OCH3O
CH3OCH2
CH2OCH3
H OH
OCH3H
HCH3O
H OCH3
CH O
Classical Method for Ring Size
Ring sizes (furanose or pyranose) have been determined using alkylation as a key step.
CH2OCH3
H OH
OCH3H
HCH3O
H OCH3
CH O
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:
OHO
HOCH2
HO
OH
O CH2
OHO
OHOH
OH
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
OBzO
BzOH2C
BzO
BzO
HO CH2
OH3CO
OAcOAc
OAc
Br
OBzO
BzOH2C
BzO
BzO
CH2
OH3CO
OAcOAc
OAc
O
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.
O
O
O
HO
O
O
HO
H3COH
OH
CH2OH
RN-Acetylgalactosamine
Polymer Protein
OCH2OH
HO
HO
OCH2OH
HO
HO
HO
H
CH3CNH
O
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.
OHO
CO2H
HOH3CCHN
OHHOHOH2C
OCO2CH2CH3H2N
H3CCHN
O
O
N-acetylneuraminic acid Oseltamivir (Tamiflu) - prodrug
O
OH
CH2O
HO
CH3CNH
O
O
O
CO2H
OHNHCCH3
HO OHCH2OH
O
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