Chapter 25: Carbohydrates

What do the - and - forms look like?

example: - and -D-glucose

Summary
The cyclic forms of carbohydrates can exist in two forms, - and - based on
the position of the substituent at the anomeric center.
The two forms are sometimes described as "anomers" since they
are isomers at the anomeric center.
To assign the cyclic form of a carbohydrate as the - or - form look at the
relative positions of the -CH2OH group and -OH (or -OR) group at the anomeric
center.
In the - form, the exocyclic O group at the anomeric center is on
the opposite face to the -CH2OH group, and

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 In the - form, the exocyclic O group at the anomeric center is on
the same face as the -CH2OH group.
If a mixture of the - and - anomers are present, then this is often
represented by using a "wavy" line to represent the bond:

In general the two forms are stable solids, but in solution they rapidly
equilibrate (see mutarotation).
The following figures shows several representations of the - and - anomers
of D-glucose.
You should Manipulate the 3D JMOL images until you can confirm the
important relationship.

-D-glucose

-D-glucose

The Anomeric Effect

In substituted cyclohexanes we learnt that the substituents usually prefer the
equatorial position due to steric effects (review ?)
In rings containing O atoms and with adjacent electronegative substituents there is a
preference for this substituent to be axial.

Do you need to review axial and equatorial terminology ?

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 This is because of an electronic effect due to an interaction of the orbitals of the ring
O and the substituent bond.
The anomeric center is important to the reactivity of carbohydrates because it is the
site at which ring opening occurs, becoming the carbonyl group, the important
functional group.

Study Tip:

The anomeric carbon or the anomeric center can be recognised by looking for the
C that is attached to two O atoms by single bonds.

Compound Line Drawing 3D Model

-D-glucose

Mutarotation : interconversion of - and - anomers

The - and - anomers of carbohydrates are typically stable solids.
However, in aqueous solution, they quickly equilibrate to an equilibrium mixture
of the two forms.
For example, in aqueous solution, glucose exists as a mixture of 36% - and
64% - (>99% of the pyranose forms exist in solution).
The equilibration occurs via the ring opening of the cyclic sugar at the anomeric
center with the acyclic form as the intermediate.

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 Or, in a simplified form with all the "extra" hydroxy groups removed:

Carbohydrate Stereochemistry
Stereochemistry was introduced as a topic in Chapter 7.
Here we will look at Fischer projections, the D-, L- notation of carbohydrates and
Haworth diagrams
It's a good idea to review the basics of these topics if you do remember them
before continuing.

Fischer projections are very commonly used to represent sugars as the provide a quick
way of representing multiple stereocenters plus they can be related to the cyclic sugar
structures reasonably easily. Note that Fischer projections of carbohydrates are typically
drawn with the longest chain oriented vertically and with the more highly oxidised C (the
carbonyl group) at the top. Here we see the Fischer projections of the simplest
carbohydrate, glyceraldehyde in its (S)-(-)- and (R)-(+)- forms:

S-(-)-glyceraldehyde R-(+)-glyceraldehyde
or or
L-glyceraldehyde D-glyceraldehyde

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The D- and L- notation is based on these structures. (Note that D- and L- means
something quite different to d- and l-).
By definition (R)-(+)-glyceraldehyde is D-glyceraldehyde and (S)-(-)-glyceraldehyde is L-
glyceraldehyde.
Other carbohydrates are defined as either D- or L- by comparing the stereochemistry at
the chirality center next to the -CH2OH group (i.e. with the chirality center furthest from
the carbonyl group or the highest numbered chirality center) with the chirality center in
glyceraldehyde.

Study Tip ?

L-glyceraldehyde has the -OH group on the left and D-glyceraldehyde on the right in
the Fischer projections of the structures.

A series of carbohydrates are shown below, decide whether they are D- or L- by

comparing them to glyceraldehyde

L-glyceraldehyde ANSWER

Haworth diagrams these are "flattened" diagrams used to represent the stereochemistry
carbohydrates, note how the relative positions of the groups in the two structures are
related.

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Haworth diagram
------------------------------------------------------

Reactions of Carbohydrates
Carbohydrates are characterised by the reactions of the component
functional groups: alcohols, aldehydes or ketones and acetals or ketals.

Alkylation of -OH
(preparation of
ethers)

Acylation of -OH
(preparation of
esters)

Reduction

Oxidation (mild)
(reducing sugars)

Hydrolysis

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Glycoside
formation

Other reactions from earlier chapters that can be applied to carbohydrates

included:

Oxidative cleavage of 1,2-diols by periodate (HIO4)

Cyanohydrin formation

Alkylation of Carbohydrates

Reaction type: Nucleophilic Substitution (SN2)

Summary
The -OH groups in carbohydrates react readily with alkylating agents
to give ethers via a simple SN2 reaction.
Methylation can be achieved using methyl iodide, CH3I, and silver
oxide Ag2O.
Benzylation can be achieved using benzyl halides (Cl, Br, I),
C6H5CH2X and a base such as NaH or Ag2O.
These reactions are often used in carbohydrate chemistry since the
products act as protecting groups for the reactive -OH functional
group.
The -OR group at the acetal center can be converted back to an -
OH with aqueous acid.

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Acylation of Carbohydrates

Reaction type: Nucleophilic Acyl Substitution

Summary
The -OH groups in carbohydrates react readily with acylating agents
such as acid halides or acid anhydrides to give esters.
Most commonly, the esters used will be an ethanoate (also
commonly known as an acetate and represented as "Ac")

This representation shows the same product as that in

the scheme at the top of the page.

These reactions are often used in carbohydrate chemistry since the

products act as protecting groups for the reactive -OH functional
group.

Reduction of Carbohydrates

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Reaction type: Nucleophilic Addition

Summary
The C=O groups in open chain forms of carbohydrates can be
reduced to alcohols by sodium borohydride, NaBH4, or catalytic
hydrogenation (H2, Ni, EtOH/H2O).
The products are known as "alditols"
LiAlH4 is usually not suitable because of its incompatibility with the
polar solvents.
Aldehydes, i.e. aldoses, are reduced to primary alcohols.
Ketones, i.e. ketoses, are reduced to secondary alcohols.

Oxidation of Carbohydrates

aldehyde carboxylate

red precipitate

Summary
As we have already seen carbohydrate C=O can be are oxidised to
carboxylic acids.
Such carbohydrates are classified as reducing sugars based on
Benedicts or Fehlings tests
Remember that aldehydes (and hence aldoses) are readily oxidised
(review ?)
In order for oxidation to occur, the cyclic form must first ring-open to
give the reactive aldehyde.
Ketoses can also be reducing sugars because they
can tautomerisation to aldoses via an enediol (review ?)

Hydrolysis

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Summary
Typical reagents : aqueous acid
Cleaves the -OR bond outside the ring at the anomeric center
replacing it with an -OH
Typically a mixture of - andisomers will be produced.
Note that this is just acetal or ketal hydrolysis (review ?)
This reaction is the reverse of that used for glycoside formation.
This reaction can be used to breakdown polysaccharides into the
component monosaccharides.
--------------------------

Glycoside formation

Summary
Typical reagents : excess ROH, acid catalyst.
Alternatively, the "ROH" can be from another saccharide so joining
two saccharide units.
Note that glycosides are just acetals or ketals (review ?)
The chemistry here is just that of simple acetals and ketals (review ?)

Carbohydrate Questions

Qu1: What type of stereochemical representation of glyceraldehyde is shown below ?

Qu2: Assign the configuration of the molecule of glyceraldehyde shown above as R or S and D or L.

Qu
Assign the configuration of the molecule of glyceraldehyde shown above as R or S and D or L.
3:

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Qu
How are the following 2 structures related ? (be as specific as you can !)
4:

Qu
For each of the following structures:
5:

(i) identify the anomeric center (ii) identify it as a hemi-acetal, acetal, kemi-ketal or ketal and
(iii) a furanose or a pyranose.

(a) (b) (c)

Qu
For each of the following structures decide whether the carbohydrate is:
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(i) an aldose or ketose, and (ii) a tetrose, pentose or hexose

(a) (b) (c)

Qu
Which of the following sugars are reducing sugars ?
7:

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 (a) (b) (c)

Anomers VS Epimers!
Anomers.
An Anomer of a saccharide only differs in its structure at the anomeric carbon.
Anomeric carbon being the functional group of the carbohydrate, which is
usually the carboxyl group attached to it.

For example, anomers of glucose are alpha-glucose and beta-glucose.

Note, the change in position of the hydroxyl group (-OH) on the anomeric
carbon( C1).

Epimers.
Epimeres, differ at only one chiral center, not the anomeric carbon.

For example, epimers of glucose.

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Note: Glucose has 5 chiral centers. Notice the change on the the second carbon,
the hydroxyl switches places with the hydrogen to give a new structure, thus
new properties.
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