09 monosaccharides and_oligosaccharides

1. Saccharides I
Monosaccharides
Derivatives of monosaccharides
Oligosaccharides
Medical Chemistry
Lecture 9 2007 (J.S.)

2. 2
Saccharides (glycids)
are polyhydroxyaldehydes, polyhydroxyketones, or
substances that give such compounds on hydrolysis.
Definition:
Classification:
POLYSACCHARIDES
polymeric
Give monosaccharides when hydrolyzed
GLYCANS
Basal units
MONOSACCHARIDES
polyhydroxyaldehydes
polyhydroxyketones
OLIGOSACCHARIDES
2 – 10 basal units
GLYCOSES (sugars)
water-soluble, sweet taste
Don't use the historical misleading term carbohydrates, please. It was primarily derived
from the empirical formula C
n
(H
2
O)
n
and currently is taken as incorrect, not recommended in
the IUPAC nomenclature (even though it can be found in numerous textbooks till now).

3. 3
Saccharides
occur widely in the nature, present in all types of cells
– the major nutrient for heterotrophs
– energy stores (glycogen, starch)
– components of structural materials (glycosaminoglycans)
– parts of important molecules
(nucleic acids, nucleotides, glycoproteins, glycolipids)
– signalling function (recognition of molecules and cells,
antigenic determinants)

4. 4
Monosaccharides
are simple sugars that cannot be hydrolyzed to simpler compounds.
Aldoses Ketoses Simple derivatives
(polyhydroxyaldehydes) (polyhydroxyketones) modified monosaccharides
are further classified according to the
number of carbon atoms in their chains:
glyceraldehyde (a triose) dihydroxyacetone
tetroses tetruloses
pentoses pentuloses
hexoses hexuloses
heptoses … heptuloses …
deoxysugars
amino sugars
uronic acids
other simple derivatives
alditols
glyconic acids
glycaric acids
Trivial names for stereoisomers
glucose (i.e. D-glucose)
fructose (i.e. D-fructose)
L-idose
L-xylulose, etc.
Systematic names
(not used in biochemistry) comprise
trivial prefixes according to the configuration:
e.g., for glucose D-gluco-hexose,
for fructose D-arabino-hexulose

5. 5
Stereoisomerism in monosaccharides
Secondary alcoholic groups CH-OH in monosaccharides are
stereogenic centres. Monosaccharides are chiral compounds
and, therefore, most of them are optically active.
Stereogenic centres are mostly carbon atoms that
bind four different groups; those atoms are oft called
"asymmetric" carbon atoms.
If there are more (n) stereogenic centres in the given molecule,
the maximal number of stereoisomers equals 2
n
.
Each of those stereoisomers has its enantiomer (mirror image) so
that there will be a maximum of 2
n
/ 2 pairs of enantiomers.
Stereoisomers that differ from the particular pair of enantiomers
are diastereomers of the pair.
In contrast to enantiomers, diastereomers differ in their
properties and exhibit different values of specific
optical rotation.

6. 6
are structural formulas that describe the configuration of particular stereoisomers.
When a plane formula of an aldose with four stereogenic centres is drawn anywhere,
e.g.,
Fischer projection formulas
an hexose
it is necessary to see a spatial arrangement of the atoms and
assess it according to the established rules:
– the least number carbon (carbonyl group in monosaccharides)
is drawn upwards,
– the carbon chain is directed downwards;
then on each stereogenic centre
– the bonds to neighbouring carbon atoms written above and
below are projected from beneath the plane of drawing
(the carbons are behind the plane),
– the horizontal bonds written to the left and right are projected
from above the plane of drawing, they are in front of plane

7. 7
Assigning configurations D- and L-
(from Latin dexter and laevus) at stereogenic centres is carried out
by comparison with the configurations of D- and L-glyceraldehyde
(see optical isomerism, lecture 5-A).
Without changing the configuration,
Fischer formulas may only be turned 180° in the plane of the paper.
Monosaccharides are classified as D- or L-sugars according to
configuration at the configurational carbon atom – the chiral
carbon with the highest numerical locant (i.e. the assymetric carbon
farthest from the aldehyde or ketone group):
D-aldose L-ketose

8. 8
D-allose D-glucose
What is that?
D-mannoseL-glucose
Enantiomers, diatereomers, epimers
L-Glucose is enantiomer of D-glucose because of
having opposite configuration at all centres of chirality.
Are there, among the following sugars, some diastereomers
of D-allose that are not epimers of it?
Is there any epimer of D-mannose?

9. 9
Stereogenic centres in molecules of monosaccharides are
the cause of their optical activity. Solutions of mono- and
oligosaccharides turn the plane of polarized light.
Optical activity is measured by using polarimeters and
usually expressed as specific optical rotation [α]
D
20
.
Dextrorotatory substances are marked (+), laevorotatory (–).

Configurations at stereogenic centres other than configurational
carbon cannot be deduced from the assignment to D- or L-sugars.
Unfortunately, configurations of several most important
monosaccharides have to be remembered.
There is no obvious relation between the assignment D- or L-
and either the values or direction of optical activity.
See tables 11 and 12.

10. 10
D-glyceraldehyde
D-erythrose D-threose
D-ribose
D-arabinose D-xylose D-lyxose
D-alloseD-altrose D-glucoseD-mannose D-gulose D-idose D-galactoseD-talose
D- Aldoses
stereochemical relations

11. 11
D-(–)-erythrose D-(–)-threose
D-(–)- arabinose D-(+)-xylose D-(–)-lyxose
D-(+)-alloseD-(+)-altrose D-(–)-guloseD-(–)-idose D-(+)-talose
D- Aldoses
optical rotation
D-(+)-glyceraldehyde
D-(–)-ribose
D-(+)-glucoseD-(+)-mannose D-(+)-galactose
(+) dextrorotatory
(–) laevorotatory

12. 12
D-(–)-erythrulose
D-(+)-xylulose
D-(+)-psicose D-(+)-sorbose D-(+)-tagatose
D- Ketoses
stereochemical relations
dihydroxyacetone
D-(–)-fructose
D-(–)-ribulose

13. 13
Cyclic forms of monosaccharides
Monosaccharides (polyhydroxyaldehydes and polyhydroxy-
ketones) undergo rapid and reversible intramolecular addition
of some properly located alcoholic group to carbonyl group
so that they form cyclic hemiacetals.
Monosaccharides exist mainly in cyclic hemiacetal forms,
in solutions the acyclic aldehydo- or keto-forms are in minority.
al-D-glucose a hemiacetal, pyranose ring

14. 14
In this way, six- or five-membered rings can originate.
In pyranoses, there is the tetrahydropyran
(oxane) ring, tetrahydrofuran (oxolane) ring
in furanoses.
In the acyclic forms, carbon of the carbonyl group is achiral,
but this carbon becomes chiral in the cyclic forms. Two
configurations are possible on this new stereogenic centre
called anomeric (or hemiacetal) carbon so that the
cyclization results in two epimers called α or β anomers:
α-anomer β-anomer

15. 15
The configuration of a- anomer is the same as the configuration at
anomeric reference carbon; in monosaccharides comprising five
and six carbon atoms (pentoses and hexoses, pentuloses and
hexuloses), the anomeric reference carbon is the configurational
carbon. α-Anomers in Fischer formulas of D-sugars have the
anomeric hydroxyl localized on the right.
The configuration of β-anomers is opposite, the anomeric hydroxyl
is written on the left in Fischer formulas of D-sugars.
The hemiacetal hydroxyl group is called the anomeric hydroxyl.

16. 16
In solutions, all five forms of a hexose or hexulose occur;
the cyclic forms usually prevail.
E.g., in the aqueous solution of D-glucose equilibrated at 20 °C, there is
approximately 62 % b-D-glucopyranose,
36 % a-D-glucopyranose,
< 0.5 % a-D-glucofuranose,
< 0.5 % b-D-glucofuranose, and
< 0.003 % aldehydo-D-glucose.
If D-glucose is crystallized from methanol or water, the pure
α-D-glucopyranose is obtained; crystallization of D-glucose from
acetic acid or pyridine gives the β-D-glucopyranose. These pure
forms exhibit mutarotation, when dissolved:
α-D-Glucopyranose just after dissolution exhibits [α]
D
20
= + 112°, the β-form
[α]
D
20 = + 19°. After certain time period, [α]
D
20
of both solutions will settle at the
same equilibrium value of + 52°. This change can be explained by opening of the
cyclic homicidal to the acyclic aldehyde. which can then recyclize to give either
the α or the β form till an equilibrium is established.

17. 17
Epimers – are those diastereomers that differ in configuration
at only one centre of chirality, they have the same configuration
at all stereogenic centres except one.
Don't confuse:
Enantiomers (optical antipodes) – stereoisomers that are not
superimposable mirror images of each other, the configurations
at all stereogenic centres are exactly opposite.
All their chemical and physical properties are the same but the
direction of optical rotation.
Anomers (α or β) represent a special kind of epimers, they
have identical configuration at every stereogenic centre but
they differ only in configuration at anomeric carbon atom.
Diastereomers – stereoisomers that are not enantiomers of
one another. They have different physical properties (melting
points, solubility, different specific optical rotations) so that
they are viewed as different chemical substances.

18. 18
Haworth projection formulas
α-D-glucopyranose
Fischer projection
Haworth projetion
(the usual basal position)
– the rings are projected as planes perpendicular to the plane of drawing,
– carbon atoms of the rings and hydrogens attached to them are not shown,
– each of the formulas can be drawn in four positions, one of which is
taken as the basal position (used preferentially).

19. 19
Rules for drawing Haworth projection formulas
(the basal position):
C
1
OH
pyranose ring of a hexose
C
1
OH
furanose ring of a hexose
C C
2
OH
furanose ring of a hexulose
– The anomeric carbon atom (C-1, in ketoses C-2) on the right;
– oxygen atom in the ring is "behind", i.e. carbon atoms are numbered
in the clockwise sense;
Then, – hydroxyl groups and hydrogens on the right in the Fischer
projection are down in the Haworth projection (below the plane
of the ring), and conversely, hydroxyls on the left in Fischer
formulas means up in Haworth formulas;
– the terminal –CH
2OH group is up for D-sugars (for L-sugars,
it is down).

20. 20
α-D-glucopyranose can be drawn in four different positions:
The basal position:Position obtained by rotation of the "model"
round a vertical axis
O
Positions obtained by tilting the "model„ over: because the numbering
of carbons is then counter-clockwise, the groups on the right in Fischer
projection as well as the terminal –CH
2
OH are up in those Haworth formulas:

or

21. 21
al-D-glucose
α-D-glucopyranoseβ-D-glucopyranose
β-D-glucofuranose α-D-glucofuranose
Four different cyclic forms of glucose
(all are depicted in the basal position)

22. 22
Four different cyclic fructose forms
α-D-fructofuranoseβ-D-fructofuranose
keto-D-fructose


β-D-fructopyranose α-D-fructopyranose
(all are depicted in the basal position)

23. 23
Conformation of pyranoses
α-D-glucopyranose-
4
C
1
β-D-glucopyranose-
4
C
1
The chair conformation of six-membered rings is more stable than the boat one.
From two possible chair conformations, that one prevails, in which most of the
voluminous groups (-OH, -CH
2
OH) are attached in equatorial positions.
steric hindrance
boat conformation
4
C
1
-chair conformation
1
C
4
-chair conformation
E.g., conformations of β-D-glucopyranose:

24. 24
Physical properties of simple sugars
Multiple hydrophilic alcoholic groups in the molecules, therefore
– non-electrolytes,
– generally crystalline solids with a high melting temperature,
– very soluble in water,
– most of them exhibit optical activity.
More or less sweet to the taste.
0.5
180
550
8000
Glucitol
Aspartame
a)
Saccharin
c)
Neotame
b)
1.0
0.5
1.5
0.3
Sucrose
Glucose
Fructose
Lactose
Synthetic sweetenersSaccharides
a)
methyl ester of the dipeptide aspartyl-phenylalanine
b)
methyl ester of the dipeptide N-(3,3-dimethylbutyl)aspartyl-phenylalanine
c)
2-sulfobenzoic imide
Sweetness related to the sweetness of sucrose

25. 25
Common reactions of monosaccharides
Carbonyl group
– is responsible for formation of cyclic forms (intramolecular hemiacetals)
– the hemiacetal (anomeric) hydroxyl may form acetals called glycosides
in reactions with alcohols, phenols, thiols, and amines
– gives sugar alcohols called alditols by reduction (hydrogenation),
– aldoses can give glyconic acids by oxidation
– can take part in the aldol condensation that gives rise to -C–C- bond.
Alcoholic groups
– give ethers by alkylation,
– form esters in reactions with acids,
– primary alcoholic group gives glycuronic acid by oxidation,
– as polyhydric alcohols, monosaccharides undergo oxidative cleavage.

26. 26
Other reactions of saccharides
– Monosaccharides are unstable in alkaline solutions, at pH < 9 may
form epimers or other isomers, at pH > 9, when heated, they are
cleaved.
– In strongly acidic solutions, pentoses and hexoses are dehydrated
to derivatives of furan-2-carbaldehyde (2-furaldehyde);
in oligosaccharides and polysaccharides, acids cleave glycosidic
bonds by hydrolysis.
– All monosaccharides and some of oligosaccharides are
reducing sugars; they are easily oxidized, e.g. in Benedict´s
test, if they have a free aldehyde group or an hemiacetal
hydroxyl (see Practicals).

27. 27
D-fructose
Reduction of monosaccharides results in formation of
D-glucose D-
glucitol
D-mannitol
alditols (sugar alcohols):

28. 28
Oxidation of monosaccharides
a g lyc o nic a c id
(aldonic)
an aldose
a g lyc a ric
a c id
(aldaric)
a g lyc u ro nic a c id
(uronic acid)

29. 29
D-Glucose
(dextrose, grape sugar) is in the form of polysaccharides
(cellulose, starch, glycogen) the most abundant sugar in the
nature.
Important monosaccharides

30. 30
D-Galactose
is the 4-epimer of glucose.
It occurs as component of lactose in milk and in dairy products
(hydrolysis of lactose in the gut yields glucose and galactose),
and as a component of glycoproteins and glycolipids.
D-Galactose
β-D-Galactopyranose

31. 31
D-Ribose
β-D-ribofuranose
β-D-ribopyranose
is the most important pentose – a component of nucleotides
and nucleic acids:

32. 32
D-fructose
D-Fructose
(laevulose, fruit sugar) is the most common ketose, present in
many different fruits and in honey. A considerable quantities of this
sugar are ingested chiefly in the form of sucrose.
β-D-fructofuranose β-D-fructopyranose

33. 33
Simple derivatives of monosaccharides
Esters
base
nucleoside 5´-phosphate fructose 1,6-bisphosphate
glucose 1-phosphate glucose 6-phosphate
with phosphoric acid are intermediates in metabolism
of saccharides, constituents of nucleotides, etc-

34. 34
Deoxysugars
Deoxyribose (2-deoxy-β-D-ribose) is a constituent of nucleotides in DNA
L-Fucose (6-deoxy-L-galactose) is, e.g., present in some determinants
of blood group antigens, and in numerous glycoproteins

35. 35
Amino sugars
are important constituents of
saccharidic components of glyco-
proteins and glycosaminoglycans.
N-acetylgalactosamine
α-D-glucosamine N-acetylglucosamine
glucosamine
(2-amino-2-deoxy-D-glucose)
fructose
CH–
CH=O
NH
2
CH–OH
CH
2
–OH
HO–CH
CH–OH
CH–OH
CH
2
–OH
HO–CH
CH–OH
C=O
CH
2
–OH
The basic amino groups –NH
2
of
amino sugars are nearly always
"neutralized“ by acetylation in the
reaction with acetyl-coenzyme A,
so that they exist as N-acetyl-
hexosamines. Unlike amines,
amides (acetamido groups) are not
basic.

36. 36
HC=O
HO–CH
HC–OH
CH
2–OH
NH
2
–CH
HC–
OH
C=O
COOH
CH
2
HC–OH
HO–CH
HC–OH
CH
2–OH
NH
2
–CH
HC–
OH
CH
3
C=O
COOH
is an aminononulose (ketone) as well as glyconic acid,
5-amino-3,5-dideoxynonulosonic acid.
It originates in the cells by condensation of pyruvate (in the form of
phosphoenolpyruvate) with mannosamine:
Neuraminic acid
mannosamine
pyruvate
neuraminic acid

37. 37
Sialic acids are constituents of saccharidic components of glycolipids
(gangliosides) and glycoproteins.
Sialic acids
is the group name used for various
acylated derivatives of neuraminic acid (N- as well as O-acylated).
The most common sialic acid is N-acetylneuraminic acid:
neuraminic acid
a sialic acid
N-acetylneuraminic acid

38. 38
Glycuronic acids (uronic acids)
D-galacturonic acidD-glucuronic acid
D-Glucuronic acid
originates in human bodies by oxidation of activated glucose (UDP-glucose).
It is a component of glycosaminoglycans in connective tissue and some
hydrophobic waste products and xenobiotics are eliminated from the body
after conjugation with glucuronic acid.
D-Galacturonic and L-iduronic acids occur also as components of numerous
glycoproteins and proteoglycans.

39. 39
Glyconic acids
are polyhydroxycarboxylic acids obtained by oxidation of the aldehyde
group of aldoses. E.g., glucose gives gluconic acid:
In the body, glucose (activated to glucose 6-phosphate) is dehydrogenated in the
enzyme-catalyzed reaction to phosphogluconolactone that gives phosphogluconate
by hydrolysis. This reaction (the initial reaction of the pentose phosphate pathway)
is very important as a source of NADPH.
D-gluconic acid
gluconate
1/2 O
2
glucose 6-phosphate
– P
D-glucono-1,5-lactone
– P
D-glucono-1,4-lactone
– P
NADP
+
NADPH+H
+

40. 40
L- Ascorbic acid
It is a weak diprotic acid (endiols are acidic), which
has outstanding reducing properties. It can be
very easily oxidized, to dehydroascorbic acid,
namely in alkaline solutions.
Ascorbate acts as a cofactor of several enzymes
and a powerful hydrophilic antioxidant. It is
essential only for humans, primates, and guinea
pigs.
– 2H– 2H
L-guloseL-gulonic acid L-gulono-1,4-lactone

L-ascorbic acid dehydro-L-ascorbic acid
(2,3-dehydro-L-gulono-1,4-lactone, vitamin C) is derived from L-gulonic acid.
Deducing of the structure of ascorbate:

41. 41
+ HO-CH
3
– H
2
O
glycosidic
bond
Glycosides
Cyclic forms of saccharides, relatively unstable hemiacetals, can
react with alcohols or phenols to form acetals called glycosides.
The hemiacetal hydroxyl group (the anomeric hydroxyl) on the
anomeric carbon is replaced by an alkoxy (or aryloxy) group.
The bond between the anomeric carbon and the alkoxy group is
called the glycosidic bond or O-glycosidic bond, at need.
Similarly, glycosidic bonds can be formed by reaction with an amino group,
N-glycosidic bonds, or with a sulfanyl group, S-glycosidic bonds
Example:
α-D-glucopyranose methanol methyl-α-D-glucopyranoside

42. 42
Names of glycosides
are formed in two different ways.
Both kinds of names have to denominate the type of glycosidic bond (α or β).
Formation of a glycosidic bond disables anomerization
on the anomeric carbon atom that takes part in the glycosidic bond.
The group that remains after taking off
the anomeric hydroxyl is called glycosyl.
E.g., α-D-glucopyranosyl (α-glucosyl):
1 The name of only the alkyl or aryl is used instead of the name of alkoxy
or aryloxy group that replaces anomeric hydroxyl and the suffix –e in the
following name of the saccharide is changed to –ide.
2 The name of a respective glycosyl is placed before the name of a
compound that gives its alcoholic or phenolic hydroxyl, sulfanyl or amino
group,.
Examples: 9-β-D-ribosyl-adenine, O-β-D-galactosyl-5-hydroxylysine.
Examples: phenyl-α-D-glucopyranoside, propyl-β-D-fructofuranoside.

43. 43
Classification of glycosides
Hologlycosides
are glycosides that give only monosaccharides by hydrolysis -
O-glycosidic bonds bind various number of monosaccharides.
Oligosaccharides – consist of as much as approximately ten
monosaccharides; the most common are disaccharides.
Polysaccharides comprise up to many thousands monosaccha-
ride units bound through glycosidic bonds. Those units are
either of the same kind in homopolysaccharides, or
may be of several kinds in heteropolysaccharides.
Heteroglycosides
in which nonsaccharidic components called aglycones or genins
are linked to saccharides through glycosidic bond.
This bond may be not only O-glycosidic but also N-glycosidic
or S-glycosidic.

44. 44
Disaccharides
are the most common disaccharides, in which two monosaccharides
are linked through glycosidic bond. There are two types of these sugars –
reducing and nonreducing disaccharides.
Reducing disaccharides
are formed by a reaction between the anomeric hydroxyl of one
monosaccharide and a alcoholic hydroxyl group of another, so
that this second monosaccharide unit retains its anomeric hydroxyl,
the reducing properties, it may anomerize and exhibits mutarotation.
Their names take the form D-glycosyl-D-glycose (with specification
of the glycoside bond).
Nonreducing disaccharides
Both anomeric hydroxyl are linked in the glycosidic bond (called
anomeric bond), neither unit has its anomeric hydroxyl. They cannot
reduce Benedict's reagent and cannot mutarotate.
Their names have the form D-glycosyl-D-glycoside.

45. 45
Maltose
Reducing disaccharides
(4-O-a-D-glucopyranosyl-D-glucopyranose, malt sugar)
is obtained by the partial hydrolysis of starch or glycogen. Two
molecules of glucose are linked through a(1→4) glycosidic bond,
further hydrolysis results in only glucose. Maltose is laevorotatory.
Crystalline maltose is the β-anomer and exhibits mutarotation, when
dissolved..
β-maltose
4-O-a-D-glucopyranosyl-β-D-glucopyranose

46. 46

Isomaltose
may be viewed as a constituent of glycogen and amylopectin placed
at branching points of the long chains connected through α(1→4) bonds.
α-isomaltose
6-O-a-D-glucopyranosyl-α-D-glucopyranose
a (1→6) glycosidic bond
6

47. 47
b
Cellobiose
(4-O-β-D-glucopyranosyl-D-glucopyranose) is obtained by the
partial hydrolysis of cellulose. Two molecules of glucose are linked
through β(1→4) glycosidic bond, further hydrolysis results in only
glucose. Cellobiose is dextrorotatory.
b
4
β-cellobiose
4-O-b-D-glucopyranosyl-β-D-glucopyranose

48. 48
Lactose
(4-O-β-D-galactopyranosyl-D-glucopyranose, milk sugar)
is the major sugar in human and cow's milk. Equimolar mixture of glucose
and galactose is obtained by hydrolysis of β(1→4) glycosidic bonds.
Lactose is dextrorotatory. Crystalline lactose is the α-anomer and
exhibits mutarotation, when dissolved.
α-lactose
4-O-b-D-galactopyranosyl-α-D-glucopyranose
β
4

49. 49
1
2
β
α
Nonreducing disaccharides
Sucrose (saccharose)
(b-D-fructofuranosyl-a-D-glucopyranoside, beet or cane sugar) is
the ordinary table sugar. Both hemiacetal hydroxyl groups of fructose
and glucose are involved in the (β2↔α1) glycosidic bond (called
occasionally anomeric glycosidic bond).
Sucrose is dextrorotatory and cannot mutarotate.
When hydrolyzed, an equimolar mixture of
glucose and fructose results that is laevorotatory
(invert sugar), because the anomers of fructose
are stronger levorotatory than the dextrorotatory
anomers of glucose.
sucrose
b-D-fructofuranosyl-a-D-glucopyranoside

50. 50
obtained X-ray structural analysis of crystalline table sugar
Real conformation of a sucrose molecule