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Home , Erythrulose, Isomaltose, Threose

Seminar 4 Definition

Saccharides (glycids) are polyhydroxyaldehydes, polyhydroxyketones, or substances that give such compounds on hydrolysis

3 Classification

Basal units Give when hydrolyzed

MONOSACCHARIDES polyhydroxyaldehydes polyhydroxyketones 2 – 10 basal units polymeric

GLYCOSES () GLYCANS water-soluble, sweet taste

Don't use the historical misleading term carbohydrates, please. It was primarily

derived from the empirical formula Cn(H2O)n and currently is taken as incorrect, not recommended in the IUPAC nomenclature (even though it can be found in numerous textbooks till now) 4 Saccharides

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

5 Monosaccharides are simple sugars that cannot be hydrolyzed to simpler compounds

Aldoses Simple derivatives (polyhydroxyaldehydes) (polyhydroxyketones) modified monosaccharides are further classified according to the deoxysugars number of atoms in their chains: amino sugars (a ) uronic acids tetruloses other simple derivatives pentuloses alditols hexuloses glyconic acids … heptuloses … glycaric acids Trivial names for stereoisomers

(i.e. D-glucose) Systematic names (i.e. D-fructose) (not used in biochemistry) comprise L- trivial prefixes according to the configuration: e.g., for glucose D-gluco-, L-, etc. for fructose D-arabino-hexulose 6 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 often called "asymmetric" carbon atoms If there are more (n) stereogenic centres in the given molecule, the maximal number of stereoisomers equals 2n Each of those stereoisomers has its enantiomer (mirror image) so that there will be a maximum of 2n / 2 pairs of enantiomers Stereoisomers that differ from the particular pair of enantiomers are of the pair In contrast to enantiomers, diastereomers differ in their properties and exhibit different values of specific optical rotation 7 Fischer projections formulas are structural formulas that describe the configuration of particular stereoisomers When a plane formula of an with four stereogenic centres is drawn anywhere

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 an hexose stereogenic centre • the bonds to neighbouring carbon atoms written above and below are projected from beneath the plane of drawing (the 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

8 Without changing the configuration, Fischer formulas may only be turned 180° in the plane of the paper.

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

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 asymmetric carbon farthest from the aldehyde or group):

D-aldose L-

9 What is that? 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- that are not epimers of it? • Is there any epimer of D-?

D-allose D-glucose L-glucose D-mannose 10 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

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 D usually expressed as specific optical rotation [α] 20. Dextrorotatory substances are marked (+), laevorotatory (–)

There is no obvious relation between the assignment D- or L- and either the values or direction of optical activity

11 D- stereochemical relations

D-glyceraldehyde

D- D-

D- D- D- D-

D-allose D- D-glucose D-mannose D- D-idose D- D- 12 D- Aldoses (+) dextrorotatory optical rotation (–) laevorotatory

D-(+)-glyceraldehyde

D-(–)-erythrose D-(–)-threose

D-(–)-ribose D-(–)- arabinose D-(+)-xylose D-(–)-lyxose

D-(+)-allose D-(+)-altrose D-(+)-glucose D-(+)-mannose D-(–)-gulose D-(–)-idose D-(+)-galactose D-(+)-talose 13 D- Ketoses stereochemical relations

dihydroxyacetone

D-(–)-

D-(–)- D-(+)-xylulose

D-(+)- D-(–)-fructose D-(+)- D-(+)-

14 Cyclic forms of monosaccharides Monosaccharides (polyhydroxyaldehydes and polyhydroxy- ) 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, ring

15 In this way, six- or five-membered rings can originate. In , there is the tetrahydropyran (oxane) ring, tetrahydrofuran (oxolane) ring in .

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 :

α- β-anomer

16 The hemiacetal hydroxyl group is called the anomeric hydroxyl

• the configuration of - 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 17 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 % -D-glucopyranose, 36 % -D-glucopyranose, < 0.5 % -D-glucofuranose, < 0.5 % -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 , when dissolved:

D α-D-Glucopyranose just after dissolution exhibits [α] 20 = + 112°, the β-form D D [α] 20 = + 19°. After certain time period, [α] 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.

18 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. 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. 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. 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. 19 Haworth projection formulas

– the rings are projected as planes perpendicular to the plane of drawing, – carbon atoms of the rings and 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)

α-D-glucopyranose

Fischer projection Haworth projetion (the usual basal position)

20 Rules for drawing Haworth projection formulas (the basal position):

– The anomeric carbon atom (C-1, in ketoses C-2) on the right; – 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 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 –CH2OH group is up for D-sugars (for L-sugars, it is down).

C C C C 1 2 1 OH OH OH

pyranose ring of a hexose ring of a furanose ring of a hexulose

21 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 –CH2OH are up in those Haworth formulas:

or

22 Four different cyclic forms of glucose (all are depicted in the basal position)

β-D-glucopyranose α-D-glucopyranose al-D-glucose

β-D-glucofuranose α-D-glucofuranose

23 Four different cyclic fructose forms (all are depicted in the basal position)

β-D-fructofuranose α-D-fructofuranose keto-D-fructose

β-D-fructopyranose α-D-fructopyranose

24 Conformation of pyranoses 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, -CH2OH) are attached in equatorial positions.

E.g., conformations of β-D-glucopyranose: steric hindrance

4 1 boat conformation C1-chair conformation C4-chair conformation

4 4 α-D-glucopyranose- C1 β-D-glucopyranose- C1

25 Reduction of monosaccharides results in formation of alditols ( alcohols):

D-glucose D-glucitol

D-fructose D-mannitol 26 Oxidation of monosaccharides

a glyconic acid (aldonic)

an aldose

a glycaric acid (aldaric)

a glycuronic acid (uronic acid)

27 Important monosaccharides

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

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

β-D-Galactopyranose D-Galactose

29 D-Ribose is the most important pentose – a component of nucleotides and nucleic acids:

β-D-ribofuranose β-D-ribopyranose

30 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

D-fructose β-D-fructofuranose β-D-fructopyranose

31 Simple derivatives of monosaccharides

Esters with phosphoric acid are intermediates in metabolism of saccharides, constituents of nucleotides, etc-

glucose 6-phosphate glucose 1-phosphate base

fructose 1,6-bisphosphate nucleoside 5´-phosphate 32 Deoxysugars

Deoxyribose (2-deoxy-β-D-ribose) is a constituent of nucleotides in DNA

L- (6-deoxy-L-galactose) is, e.g., present in some determinants of blood group antigens, and in numerous glycoproteins

33 Amino sugars are important constituents of CH=O CH2–OH saccharidic components of glyco- C=O CH– NH proteins and glycosaminoglycans. 2 HO–CH HO–CH The basic amino groups –NH of amino 2 CH–OH sugars are nearly always "neutralized“ CH–OH by acetylation in the reaction with CH–OH CH–OH acetyl-coenzyme A, CH2–OH CH2–OH so that they exist as N-acetyl- fructose glucosamine hexosamines. Unlike amines, amides (2-amino-2-deoxy-D-glucose) (acetamido groups) are not basic.

α-D-glucosamine N-acetylglucosamine N-acetylgalactosamine 34 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:

pyruvate COOH COOH C=O C=O CH 3 C H 2 HC=O HC–OH

NH2–CH NH2–CH HO–CH HO–CH HC–OH HC–OH HC–OH HC–OH neuraminic acid

CH2–OH CH2–OH mannosamine

35 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 sialic acid N-acetylneuraminic acid

Sialic acids are constituents of saccharidic components of glycolipids (gangliosides) and glycoproteins 36 Glycuronic acids (uronic acids)

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-glucuronic acid D-galacturonic acid

D-Galacturonic and L-iduronic acids occur also as components of numerous glycoproteins and proteoglycans.

37 Glyconic acids are polyhydroxycarboxylic acids obtained by oxidation of the aldehyde group of aldoses. E.g., glucose gives gluconic acid:

1/2 O2

D-gluconic acid gluconate

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.

– P – P – P NADP+ NADPH+H+

glucose 6-phosphate D-glucono-1,5-lactone D-glucono-1,4-lactone

38 L- Ascorbic acid (2,3-dehydro-L-gulono-1,4-lactone, vitamin C) is derived from L-gulonic 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.

Deducing of the structure of ascorbate:

– 2H – 2H

L-gulose L-gulonic acid L-gulono-1,4-lactone L-ascorbic acid dehydro-L-ascorbic acid

39 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 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: glycosidic bond

– H2O + HO-CH3

α-D-glucopyranose methanol methyl-α-D-glucopyranoside

40 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 . 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.

41 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 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.

42 Reducing disaccharides (4-O--D-glucopyranosyl-D-glucopyranose, malt sugar) is obtained by the partial hydrolysis of starch or glycogen. Two molecules of glucose are linked through (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--D-glucopyranosyl-β-D-glucopyranose

43 may be viewed as a constituent of glycogen and placed at branching points of the long chains connected through α(1→4) bonds.

 (1→6) glycosidic bond

6

α-isomaltose 6-O--D-glucopyranosyl-α-D-glucopyranose

44

(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.

4

β-cellobiose 4-O--D-glucopyranosyl-β-D-glucopyranose 45 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.

4

β

α-lactose 4-O--D-galactopyranosyl-α-D-glucopyranose

46 Nonreducing disaccharides Sucrose (saccharose) (-D-fructofuranosyl--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 -D-fructofuranosyl--D-glucopyranoside 1 α

Sucrose is dextrorotatory and cannot mutarotate. β When hydrolyzed, an equimolar mixture of 2 glucose and fructose results that is laevorotatory (invert sugar), because the anomers of fructose are stronger levorotatory than the dextrorotatory anomers of glucose.

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

48 Seminar problems answers

Q1. For each of followings structure decide whether the carbohydrates is: an aldose or ketose and , pentose or hexose.

(a) (b) (c)

Aldose Ketose Aldose Hexose Hexose Tetrose Q2. Easy – memorising

Q3. Easy – memorising

Q4. The followings questions apply to the sugar A.

a) Ketose b) Anomeric carbon c) OH C4 d) This is β (D) Q5. Use the following structures in answering the next questions.

a) L-sugars: B and G – last asymatric atom (the highest locant) is 4 (OH up means it is on the left) b) α-anomers: D, E c) Reducing sugars: A, C, D, F, G d) Derived from the same sugar: A and F, E and H e) Deoxy sugars: Only C f) Names od „D” sugar: α- and β-D-fructofuranose

Q6. Easy – memorising

Q7. Easy – memorising

Q8. Which one of the followings would show mutarotation when dissolved in water? the following structures in answering the next questions.

Mutarotation: Only C (it has „free” anomeric carbon)

Q9. Easy – memorising

Q10. Which of the following sugars are reducing sugars?

Reducing sugars

Q11. Easy – memorising Q12. Easy – see the lecture

Q13. A 4 g sugar cube (Sucrose: C12H22O11) is dissolved in a 350 ml teacup of 80°C water. What is the percent composition by mass of the sugar solution? Given: Density of water at 80 °C = 0.975 g/ml

4 푔 퐶푝 = 푔 ∙ 100% 4 푔 + 350 푚푙 ∙ 0,975 푚푙