09 monosaccharides and_oligosaccharides


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09 monosaccharides and_oligosaccharides

  1. 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 tetr ul oses pentoses pent ul oses hexoses hex ul oses heptoses … hept ul oses … 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. 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-allose that are not epimers of it? Is there any epimer of D-mannose? D- allose D- glucose D- mannose L- glucose
  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- allose D- altrose D- glucose D- mannose D- gulose D- idose D- galactose D- talose D- Aldoses stereochemical relations
  11. 11. D- ( – ) - erythrose D- (–) - threose D- ( – ) - arabinose D- (+) - xylose D- ( – ) - lyxose D- (+) - allose D- (+) - altrose D- ( – ) - gulose D- ( – ) - idose D- ( + ) - talose D- Aldoses optical rotation D- (+) - glyceraldehyde D- ( – ) - ribose D- (+) - glucose D- (+)- 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- keton e s) 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 th at the cyclization results in two epimers called α or β anomers : α -anomer β -anomer
  15. 15. 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. 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 %  - 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 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 – 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 ). Fischer projection Haworth projetion (the usual basal position)
  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 &quot; behind &quot;, 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 2 OH 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 &quot;model&quot; round a vertical axis Positions obtained by tilting the &quot;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 -gluco pyranose β - D -gluco pyranose β - D -gluco furanose α - D -gluco furanose Four different cyclic forms of glucose (all are depicted in the basal position)
  22. 22. Four different cyclic fructose forms α - D -fructo furanose β - D -fructo furanose β - D -fructo pyranose α - D -fructo pyranose (all are depicted in the basal position) keto - D- fructose
  23. 23. 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, -CH 2 OH) are attached in equatorial positions. steric hindrance E.g., conformations of β- D -glucopyranose : α - D -glucopyranose - 4 C 1 β - D -glucopyranose - 4 C 1 boat conformation 4 C 1 -chair conformation 1 C 4 -chair conformation
  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. 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 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 sweeteners Saccharides
  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 m onosaccharides 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 alditols (sugar alcohols): D- glucose D- glucitol D- mannitol
  28. 28. Oxidation of monosaccharides a glyconic acid (aldonic) an aldose a glycaric acid (aldaric) a glycuronic acid (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 &quot; 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 C H 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-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. D -galacturonic acid D -glucuronic acid
  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 + NADP H + 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- gulose L- 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 T he 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 - glycos yl - D - glycos e (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 - glycos yl - D - glycos ide .
  45. 45. Maltose 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
  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-  - D -glucopyranosyl- α- D -glucopyranose  (1 ->6 ) glycosidic bond 6
  47. 47.  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 ) glycosid ic bond , further hydrolysis results in only glucose. Cellobiose is dextrorotatory.  4 β - cellobiose 4-O-  - 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-  - D -galactopyranosyl- α- D -glucopyranose β 4
  49. 49. 1 2 β α 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 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  - D -fructofuranosyl-  - D -glucopyranos ide
  50. 50. obtained X-ray structural analysis of crystalline table sugar Real conformation of a sucrose molecule