Practice Question:

Classify the following monosaccharides.

OH O O
(a) HO H (b) HO OH
OH OH
.
The pre-reading for this lecture covered:

Carbohydrates introduction

Classification of carbohydrates
CHEM 110 [2019]
CHEMISTRY OF THE LIVING WORLD

Block 6 - Units 3 to 7
Carboxylic acids and derivatives, amines,
peptides/proteins and carbohydrates

Lecturer: Assoc. Prof. David Barker

Room 627B, 6th floor building 301
Phone extension 89703
d.barker@auckland.ac.nz
3.2 Configuration of Monosaccharides
3.2.1 Stereoisomerism in Monosaccharides

Recall (block 1):

• Stereoisomers: same molecular formula, same connectivity,
different arrangement in space. Interconversion requires bond-
breaking and forming.
• Enantiomers: stereoisomers that are also mirror images of each
other.
• Diastereomers: stereoisomers that are NOT mirror images of
each other.
For a compound with multiple stereocentres, ALL stereocentres must
be reversed to generate the enantiomer.
Reversing some but not all stereocentres gives a diastereomers.
• e.g.
OH O OH O OH O
(a) HO OH OH OH
(b) HO (c) HO
OH OH – OH
OH OH OH

(a) and (b) – enantiomers

(a) and (c) – diastereomers
(b) and (c) – diastereomers
 Consider aldoses as an example:
O OH O OH O OH OH O
HO HO
HO H H HO H H
OH OH OH OH OH OH
triose tetrose pentose hexose

–
Aldose Stereo- Stereo- pairs of
centres isomers enantiomers

aldotriose 1 2 1
aldotetrose
2 4 2
aldopentose
3 8 4
aldohexose
4 16 8

Mathematically, no of stereoisomers = 2n
where n = number of stereocentres
3.2.2 D/L Sugars
D,L notation is still in common usage for sugars.

The notation is dertived from glyceraldehyde as (R)

glyceraldehyde rotates plane polarised light clockwise
(dextrorotary, D) and (S)-glyceraldehyde rotates it anticlockwise
(laevorotary, L).

HO H
OH
D-glyceraldehyde

For all other carbohydrates the D and L notations may have no

relation to the direction in which a given sugar rotates plane
polarized light.
For sugars containing multiple stereocentres D/L notation is
determined by the stereochemistry of the group furthest from
the C=O group.

OH O
In D sugars, this stereocentre is (R) OH
HO
In L sugars, this stereocentre is (S) OH OH

Note: biochemists often depict sugars using an alternate

method of showing stereochemistry, called a Fischer
projection. This is increasingly rare in chemistry and is no
longer covered in this course.
 Practice Question:

How many stereoisomers are possible for the sugar below.

Draw one pair of enantiomers.
OH O
OH
HO
OH OH
.

Challenge: Label each of your enantiomers as D or L.

3.3 Cyclic Structure of Monosaccharides

We saw in the last lecture that aldehydes and ketones react with
alcohols to form hemiacetals (and acetals).
Sugars contain both carbonyl (aldehyde or ketone) and alcohol
groups and can form hemiacetals internally – a cyclic hemiacetal.

OH
OH OH O
O
HO HO OH
H
OH OH OH
OH

In aqueous solution, sugars exist in equilibrium between the open-

chain and cyclic forms.
Sugars have multiple alcohol groups – but five and six-membered
cyclic hemiacetals are most common due to their stability.
OH
OH OH O
O
HO HO OH
H
OH OH OH
OH

Like cyclohexanes (block 1) – 6-membered cyclic hemiacetals adopt

chair conformations.

An assessment of the relative stability of these chair conformers can

be made based on how many groups are in the equatorial position.
3.3.1 Anomers

Forming the cyclic hemiacetal does not change the stereochemistry

of the existing stereocentres.
OH
OH OH O
O
HO HO OH
H
OH OH OH
OH
However, at C-1 a new stereocentre is formed.
OH OH OH
O OH O
HO HO HO OH
H
OH OH O OH
OH OH OH OH

The two cyclic hemiacetal forms are diastereomers. Diastereomers

that differ only at one carbon are called anomers.
To differentiate between the two possible anomers:

The -anomer has the C1 –OH and the C5 CH2OH groups trans

The -anomer has the C1 –OH and the C5 CH2OH groups cis

OH OH OH
O OH O
HO HO HO OH
H
OH OH O OH
OH OH OH OH

In aqueous solution, this system is in equilibrium, and the relative

amount of each anomer will depend of the stability of it’s lowest
energy chair conformer.
3.3.2 Monosaccharide Anomers and Mutorotation

Recall, the two possible anomers (and the open chain form) exist in
equilibrium in aqueous solution. For glucose:
OH OH OH

HO O OH O
HO HO OH
HO H
HO HO
OH OH O OH
OH

[]D : +113 []D : +19

If you dissolve either pure anomer in water and allow it to reach

equilibrium, the solution will have a specific rotation ([]D ) of +53.
This corresponds to an equilibrium ratio of 36:64 of the two anomers.
This ‘scrambling’ of the anomeric stereocentre in solution is called
mutorotation.
3.4 Reactions of Monosaccharides
3.4.1 Ester and ether formation

The –OH groups in a carbohydrate, including the anomeric carbon,

can be converted to esters and ethers.

CH2OH
HO O
HO OH
(CH3CO)2O
CH3I/Ag2O HO
O
O CH2OCCH3
CH2OCH3 CH3CO O
CH3O O CH3CO OCCH3
CH3O OCH3 O CH CO
3
O
CH3O O
Both of these reactions affect ALL the free –OH groups in the
molecule.

The anomeric –OH can also react selectively to form an acetal.

CH2OH CH3OH/H+ CH2OH

HO O HO O
HO OH HO OCH3
HO HO
hemiacetal acetal
[methyl -D-glucopyranoside]

This is exactly analogous to forming acetals from hemiacetals in non-

cyclic compounds.

The acetal of a sugar is called a glycoside.

Glycosides (like all acetals) are stable to water and are not in
equilibrium with their open chain form.
Thus they do not exhibit mutorotation.

CH2OH CH3OH/H+ CH2OH

HO O HO O
HO OH H O/H+ HO OCH3
HO 3 HO
hemiacetal acetal
[methyl -D-glucopyranoside]

Again, like acetals, a glycoside can be converted back to a free

monosaccharide by treatment with aqueous acid.
3.4.2 Polysaccharide Formation

If the acetal is formed with the –OH from another sugar, a

disaccharide is formed.

HO OH OH HO OH OH
O HO OH O HO
+ HO OH
HO O O O
OH HO
OH OH
OH OH
galactose glucose lactose

This bond is called a glycosidic bond or glycosidic linkage.

Many biologically important molecules contain glycosidic linkages

Sucrose
Maltose

Lactose Digoxin
Concepts applied from other parts of the course:
• Enantiomers and diastereomers (Block 1, lectures 4/5)
• Assigning R/S to stereocentres (Block 1, lectures 4/5)
• Conformers – chair conformers, including stability analysis (block
1, lecture 3)
• Acetals and hemiacetals – (Block 6, lecture 3)
• Ethers (by nucleophilic substitution) (Block 4, lecture 5, Block 6,
lecture 2)
• Esters (will be covered in Block 6, Lecture 6)
New Terminology
• Aldo/keto classification
• D/L notation – corresponds to R/S notation for the stereocentre furthest from
the C=O
•  notation – corresponds to trans/cis notation specifically comparing the
groups at C1 (hemiacetal) and C5
• Anomer – Diastereomers that differ at only one chiral carbon.
• Anomeric carbon (sugar) – the hemiacetal carbon (the one with 2 C-O bonds).
• Glycoside – the acetal of a sugar
• Glycosidic bond – bond between the anomeric carbon of one sugar and the
OH group of another. Links two sugars together.
• Mutorotation – scrambling of stereochemistry at the anomeric carbon when a
single anomer of a sugar is dissolved in water. Only happens to hemiacetals.