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 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


CH O

CH2OH

HHO

H OH

D-Erythrose D-Threose

D-Erythrose and D-threose are diastereomers.

CH O

CH2OH

H OH

H OH


L-Erythrose D-Threose

L-Erythrose and D-threose are diastereomers.

CH O

CH2OH

HHO

H OH

CH O

CH2OH

HHO

HO H


D-Threose

D-Threose and L-threose are enantiomers.

L-Threose

CH O

CH2OH

HHO

H OH

CH O

CH2OH

OHH

HHO


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


CH O

CH2OH

H OH

All Allose

Altruists Altrose

Gladly Glucose

Make Mannose

Gum Gulose

In Idose

Gallon Galactose

Tanks Talose


CH O

CH2OH

H OH

Allose

Altrose

Glucose

Mannose

Gulose

Idose

Galactose

Talose


CH O

CH2OH

H OH

Allose

Altrose

Glucose

Mannose

Gulose

Idose

Galactose

Talose


CH O

CH2OH

H OH

OHH

Allose

Altrose

Glucose

Mannose

Gulose

Idose

Galactose

Talose


CH O

CH2OH

H OH

HO H

Allose

Altrose

Glucose

Mannose

Gulose

Idose

Galactose

Talose


CH O

CH2OH

H OH

OHH

Allose

Altrose

Glucose

Mannose

Gulose

Idose

Galactose

Talose


CH O

CH2OH

H OH

OHH

OHH

Allose

Altrose

Glucose

Mannose

Gulose

Idose

Galactose

Talose


CH O

CH2OH

H OH

OHH

HO H

Allose

Altrose

Glucose

Mannose

Gulose

Idose

Galactose

Talose


CH O

CH2OH

H OH

HO H

Allose

Altrose

Glucose

Mannose

Gulose

Idose

Galactose

Talose


CH O

CH2OH

H OH

HO H

H OH

Allose

Altrose

Glucose

Mannose

Gulose

Idose

Galactose

Talose


CH O

CH2OH

H OH

HO H

HHO

Allose

Altrose

Glucose

Mannose

Gulose

Idose

Galactose

Talose


CH O

CH2OH

H OH

OHH

OHH

Allose

Altrose

Glucose

Mannose

Gulose

Idose

Galactose

Talose


CH O

CH2OH

H OH

OHH

OHH

OHH

Allose

Altrose

Glucose

Mannose

Gulose

Idose

Galactose

Talose


CH O

CH2OH

H OH

OHH

OHH

HO H

Allose

Altrose

Glucose

Mannose

Gulose

Idose

Galactose

Talose


CH O

CH2OH

H OH

OHH

HO H

Allose

Altrose

Glucose

Mannose

Gulose

Idose

Galactose

Talose


CH O

CH2OH

H OH

OHH

HO H

OHH

Allose

Altrose

Glucose

Mannose

Gulose

Idose

Galactose

Talose


CH O

CH2OH

H OH

OHH

HO H

HO H

Allose

Altrose

Glucose

Mannose

Gulose

Idose

Galactose

Talose


CH O

CH2OH

H OH

HO H

H OH

Allose

Altrose

Glucose

Mannose

Gulose

Idose

Galactose

Talose


CH O

CH2OH

H OH

HO H

H OH

OHH

Allose

Altrose

Glucose

Mannose

Gulose

Idose

Galactose

Talose


CH O

CH2OH

H OH

HO H

H OH

HO H

Allose

Altrose

Glucose

Mannose

Gulose

Idose

Galactose

Talose


CH O

CH2OH

H OH

HO H

HHO

Allose

Altrose

Glucose

Mannose

Gulose

Idose

Galactose

Talose


CH O

CH2OH

H OH

HO H

HHO

OHH

Allose

Altrose

Glucose

Mannose

Gulose

Idose

Galactose

Talose


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


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


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


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


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


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



O

OCH3

CH3O

CH3OCH3O

CH3OCH2

H2O

H+

(mixture of + )

O

OHCH3O

CH3OCH3O

CH3OCH2



(mixture of + )

O

OHCH3O

CH3OCH3O

CH3OCH2

CH2OCH3

H OH

OCH3H

HCH3O

H OCH3

CH O



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

chapter 23 carbohydrates

Documents

glyceraldehyde glyceraldehyde

monosaccharide units

chain length

carbohydrate configurationsthe

simpler carbohydrate

configuration of highest

numbered stereogenic

classes of carbohydrates23