1. LECTURE 14
THEME: Carbohydrates. Monosacchrides. Structure. Isomery. Reactionary ability of the monosaccharides.
associate. prof. Ye. B. Dmukhalska, assistant. I.I. Medvid

2. Outline: Classification of monosaccharides. Carbohydrates.
Classification of carbohydrates.
Chirality: handedness in molecules. Stereoisomers. Fisher Projections.
Classification of monosaccharides.
Reactions of monosaccharides.
Biologically important monosaccharides.

3. Examples of carbohydrates
IUPAC nomenclature doesn't use for carbohydrates, trivial nomenclature uses for them.

4. Carbohydrates are polyhydroxy aldehydes, polyhydroxy ketones, or compounds that yield such substances upon hydrolysis. The carbohydrate glucose is а polyhydroxy aldehyde, and the carbohydrate fructose is а polyhydroxy ketone. А striking structural feature of carbohydrates is the large number of functional groups present. In glucose and fructose there is а functional group attached to each carbon atom.

5. A person’s left and right hands are not superinposable upon each other.

6. Chirality. Objects that cannot be superimposed upon their mirror image are said to be chiral objects. А chiral object is an object that is not identical to its mirror image. Your hands and feet are chiral objects, as are gloves and shoes. Objects that can be superimposed upon their mirror images are achiral. An achiral object is identical to its mirror image. Achiral objects include tube socks, solid-colored ties and Т-shirts. Molecules, like larger objects, can be chiral or achiral. А simple example of а chiral molecule is the trisubstituted methane bromochloroiodomethane.
The simplest example of а chiral carbohydrate is the three-carbon molecule glyceraldehyde.

7. 2-butanol
1-chloto-1-iodoethane
3-methylhexane
Organic molecules, especially carbohydrates, may contain more than one chiral center. For example, the following carbohydrate has two chiral centers.

8. Handedness (D and L configuration) is determined by the configuration at the highest-numbered chiral center (for pentoses – C4, for hexoses – C5).

9. Majority of monosaccharides refer to D-row.

10. Stereoisomers can be subdivided into two types: enantiomers and diastereomers.
Enantiomers are stereoisomers whose molecules are nonsuperimposable mirror images of each other. Left- and right-handed forms of а molecule with а single chiral center are enantiomers.
Diastereomers are stereoisomers whose molecules are not mirror images of each other. Cis - trans isomers (of both the alkene and the cycloalkane types) are diastereomers. We will see additional examples of carbohydrate diastereomers in the next section. Stereoisomers that are not enantiomers are diastereomers; they must be one or the other.
Diastereomers
Enantiomers

11. Fisher Projections. Drawing three-dimensional representations of chiral molecules, can be both time-consuming and awkward. Fischer projections represent а method for giving molecular chirality specifications in two dimensions. А Fisher projection is а two-dimensional notation showing the spatial arrangement of groups about chiral centers in molecules. In а Fischer projection, а chiral center is represented as the intersection of vertical and horizontal lines. The atom at the chiral center, which is almost always carbon, is not explicitly shown.

12. The tetrahedral arrangement of the four groups attached to the atom at the chiral center is governed by the following conventions: (1) Vertical lines from the chiral center represent bonds to groups directed into the printed page. (2) Horizontal lines from the chiral center represent bonds to groups directed out of the printed page Fischer projection
Our immediate concern is Fisher projections for monosaccharides. Such projections have the monosaccharide carbon chain positioned vertically with the carbonyl group (aldehyde or ketone) at or near the top.

13. The smallest monosaccharide that has а chiral center is the compound glyceraldehydes (2,3-dihydroxypropanal). The structural formula and Fischer projections for the two enantiomers of glyceraldehyde are:
D-glyceraldehyde L-glyceraldehyde
The handedness (right and left) of these two enantiomers is specified by using the designations D and L. The enantiomer with the chiral center - ОН group on the right in the Fischer projection is by definition the right-handed isomer (D-glyceraldehyde), and the enantiomer with the chiral center - ОН group on the left in the Fisher projection is by definition the left-handed isomer (L-glyceraldehyde).

14. We now consider Fisher projections for the compound 2,3,4-trihydroxybutanal, а monosaccharide with four carbons and two chiral centers.There are four stereoisomers for this compound - two pairs of enantiomers:
In the first enantiomeric pair, both chiral center - ОН groups are on the same side of the Fischer projection, and in the second enantiomeric pair, the chiral center - ОН groups are on opposite sides of the Fisher projection. These are the only - ОН group arrangements possible. A B C D
First enantiomeric pair
Second enantiomeric pair

15. The D, L system used to designate the handedness of glyceraldehyde enantiomers is extended to monosaccharides with more than one chiral center in the following manner. The carbon chain is numbered, starting at the carbonyl group end of the molecule, and the highest-numbered chiral center is used to determine D or L configuration.
The D, L nomenclature gives the configuration (handedness) only at the highest-numbered chiral center. The configuration at other chiral centers in а molecule is accounted for by assigning а different common name to each pair of D, L enantiomers. In our present example, compounds А and В (the first enantiomeric pair) are D-erythrose and L-erythrose; compounds С and D (the second enantiomeric pair) are D-threose and L-threose. A B C D
D- isomer L-isomer
D-isomer L- isomer

16. Monosaccharides are also often called sugars
Monosaccharides are also often called sugars. Hexoses are six-carbon sugars, pentoses five-carbon sugars, and so on. The word sugar is associated with "sweetness," and most (but not all) monosaccharides have а sweet taste. The designation sugar is also applied to disaccharides, many of which also have а sweet taste. Thus sugar is а general designation for either а monosaccharide or а disaccharide. The simplest aldose and ketose are the trioses glyceraldehyde and dihydroxyacetone.
The D and L designations specify the configuration at the highest-numbered chiral center in а monosaccharide. The configurations about other chiral centers are accounted for by assigning а different common name to each pair of D and L enantiomers. This naming system, for simple aldoses, is given
glyceraldehydes
dihydroxycaetone

18. The L forms are mirror images of the molecules shown
The L forms are mirror images of the molecules shown. А major difference between glyceraldehyde and dihydroxyacetone is that the latter does not possess а chiral carbon atom. Thus, D and L forms are not possible for dihydroxy acetone. This reduces by half (compared with aldoses) the number of stereoisomers possible for ketotetroses, ketopentoses, and ketohexoses. An aldohexose has four chiral carbon atoms, but а ketohexose has only three. atoins.

19. Structure of monosaccharides
Aldehyde react with alcohols with formation of hemiacetals:
Monosaccharides as polyhydroxyaldehydes or polyhydroxyketons also form cyclic hemiacetals by intermolecular interaction between carbonyl and spatially approximate alcohol group. These interaction cases formation of five- and sixmember cycles. Sixmember cycle called pyranose and fivemember cycle – furanose.

20. Pyranose cycle forms after interaction of oxo-group with hydroxy-group at C5 carbon atom of aldohexoses or C6 carbon atom of ketohexoses.
Furanose cycle forms after interaction of oxo-group with hydroxy-group at C4 carbon atom of aldohexoses or C5 carbon atom of ketohexoses.

21. Shown higher formulas of monosaccharides name formulas of Colly-Tollens.

22. Cyclic forms of monosaccharides.
So far in this chapter, the structures of monosaccharides have been depicted as open-chain polyhydroxy aldehydes or ketones. However, experimental evidence indicates that for monosaccharides containing five or more carbon atoms, such open-chain structures are actually in equilibrium with two cyclic structures, and the cyclic structures are the dominant forms at equilibrium. The cyclic forms of monosaccharides result from the ability of their carbonyl group to react intramolecularly with а hydroxyl group. The result is а cyclic hemiacetal or cyclic hemiketal. Such an intramolecular cyclization reaction for D-glucose is shown:

23. In an aqueous solution of β-glucose, а dynamic equilibrium exists among the , , and open-chain forms, and there is continual interconversion among them. For example, a freshly mixed solution of pure -D-glucose slowly converts to а mixture of both - and -D-glucose by an opening and а closing of the cyclic structure. When equilibrium is established, 63 % of the molecules are -D-glucose, 37 % are -D-glucose, and less than 0.01 % are in the open-chain form. Intramolecular cyclic hemiacetal formation and the equilibrium between forms associated with it is not restricted to glucose. All aldoses with five or more carbon atoms establish similar equilibria, but with different percentages of the alpha, beta, and open-chain forms. Fructose and other ketoses with а sufficient number of carbon atoms also cyclize; here, cyclic hemiketal formation occurs. Galactose, like glucose, forms а six-membered ring, but both D-fructose and D-ribose form а five-membered ring.
D-Fructose cyclization involves carbon-2 (the keto group) and carbon-5, which results in two CH2OH groups being outside the ring (carbons 1 and 6). D-Ribose cyclization involves carbon-1 (the aldehyde group) and carbon-4.
D-fructose
D-ribose

24. Haworth projection formulas.
The structural representations of the cyclic forms of monosaccharides found in the previous section are examples of Haworth projection formulas. А Haworth projection is а of а carbohydrate. In а Haworth projection, the hemiacetal ring system is viewed "edge on" with the oxygen ring atom at the upper right (six-membered ring) or at the top (five-membered ring).
The D or L form of а monosaccharide is determined by the position of the terminal СН2ОН group on the highest-numbered ring carbon atom. In the в form, this group is positioned above the ring. In the ь form, which is not usually encountered in biological systems, the terminal CH2OH group is positioned below the ring.

25.  or  configuration is determined by the position of the -ОН group on carbon-1 relative to the CH2OH group that determines D or L series.
-D-Monosaccharide -D-Monosaccharide -L-Monosaccharide
Where  or  configuration does not matter, the -ОН group on carbon-1 is placed in a horizontal position, and а wavy line is used as the bond that connects it to the ring.

26. The specific identity of а monosaccharide is determined by the positioning of the other: - ОН groups in the Haworth projection. Any - ОН group at а chiral center that is to the right in а Fisher projection formula points down in the Haworth projection. Any group to the left in а Fisher projection points up in the Haworth projection. The following is a matchup between Haworth projection and Fisher projection.
-form -form

27. Transition from Colly-Tollens formulas to Haworth formulas

29. Tautomery This kind of tautomery called cyclo-oxo-tautomery
In crystal state monosaccharides have cyclic structure. In water solution monosaccharides have five tautomeric forms – open form, α- and β-pyranose, α- and β-furanose.
This kind of tautomery called cyclo-oxo-tautomery

31. Conformation of monosaccharides
Furanose forms of monosaccharides have plain structure, for pyranoses more profitable is form of armchair.
There are two kinds of armchair conformation of pyranose forms. More stable is conformation with maximal number of substitutions (OH- and CH2OH-groups) in equatorial locations.
For aldohexose more profitable is form of armchair

32. Transition from Haworth formulas to armchair configuration:

33. Methods of getting of monosaccharides
1. In green plants by photosynthesis:
2. Disaccharides, oligosaccharides, and polysaccharides can be broken down to monosaccharide subunits by hydrolysis.
3. Disintegration by Ruff. By these method we can get shorter carbon chain based on oxidation of monosaccharides.

34. 4. Cyanhydrinic synthesis
4. Cyanhydrinic synthesis. By these method we can get bigger carbon chain:

35. 5. Reactions of monosaccharides.
1.The reduction of D-fructose forms D-mannitol and D-glucitol, the C-2 epimer of D-mannitol. D- lucitol—also called sorbitol—is about 60% as sweet as sucrose. It is found in plums, pears, cherries, and berries and is used as a sugar substitute in the manufacture of candy.

36. 1.Reduction. The carbonyl group present in а monosaccharide (either an aldose or а ketose) can be reduced to а hydroxyl group, using hydrogen as the reducing agent. For aldoses and ketoses, the product of the reduction is the corresponding polyhydroxy alcohol, which is sometimes called а sugar alcohol. For example, the reduction D-glucose gives D-glucitol.
D-Glucitol is also known by the common name D-sorbitol. Hexahydroxy alcohols such as D-sorbitol have properties similar to those of the trihydroxy alcohol glycerol. These alcohols are used as moisturizing agents in foods and cosmetics because of their affinity for water. D-Sorbitol is also used as а sweetening agent in chewing gum; bacteria that cause tooth decay cannot use polyalcohols as food sources, as they can glucose and many other monosaccharides.

38. 2. Oxidation. Monosaccharide oxidation can yield three different types of oxidation products. The oxidizing agent used determines the product. Weak oxidizing agents, such as Tollens, Fehling's, and Benedict's solutions, oxidize the carbonyl group end of а monosaccharide to give an -onic acid. Oxidation of the aldehyde end of glucose produces gluconic acid, and oxidation of the aldehyde end of galactose produces galactonic acid. The structures involved in the glucose reaction are:
Because monosaccharides act as reducing agents in such reactions, they are called reducing sugars. With Tollens solution, glucose reduces Ag+ ion to Ag, and with Benedict's and Feling's solutions, glucose reduces Cu2+ ion to Cu+ ion. А reducing sugar is a carbohydrate that gives a positive test with Tollens, Benedict's and Feling's solutions. All monosaccharides are reducing sugars.

39. Tollens, Feling's, and Benedict's solutions can be used to test for glucose in urine, а symptom of diabetes. For example, using Benedict's solution, we observe that if no glucose is present in the urine (а normal condition), the Benedict's solution remains blue. The presence of glucose is indicated by the formation of а red precipitate. Testing for the presence of glucose in urine is such а common laboratory procedure that much effort has been put into the development of easy-to-use test methods. Strong oxidizing agents can oxidize both ends of а monosaccharide at the same time (the carbonyl group and the terminal primary alcohol group) to produce а dicarboxylic acid. Such polyhydroxy dicarboxylic acids are known as -aric acids. For glucose, such an oxidation produces glucaric acid.

40. At selective oxidation primary alcohol group in aldoses molecules form uronic acids:

41. Although it is difficult to do in the laboratory, in biological systems enzymes can oxidize the primary alcohol end of an aldose such as glucose, without oxidation of the aldehyde group, to produce а -uronic acid. For glucose, such an oxidation produces D-glucuronic acid.
D-Glucitol is also known by the common name D-sorbitol. Hexahydroxy alcohols such as D-sorbitol have properties similar to those of the trihydroxy alcohol glycerol. These alcohols are used as moisturizing agents in foods and cosmetics because of their affinity for water. D-Sorbitol is also used as а sweetening agent in chewing gum; bacteria that cause tooth decay cannot use polyalcohols as food sources, as they can glucose and many other monosaccharides.
D-Glucose
D-Glucitol

42. 3. Transformation of monosaccharides by action of alkali (epimerization)

43. 4. Ozazone formation.
The tendency of monosaccharides to form syrups that do not crystallize made the purification and isolation of monosaccharides difficult. Emil Fisher found that when phenylhydrazine is added to an aldose or a ketose, a yellow crystalline solid that is insoluble in water is formed. He called this derivative an ozazone (“ose” for sugar; “azone” for hydrazone). Ozazones are easily isolated and purified and were once used extensively to identify monosaccharides

44. Mechanism of reaction of ozazone formation

45. By the action of conc. HCl or heating wjth benzaldehyde forms ozones (ketoaldehydes).
At the reduction of ozones forms ketoses.

46. 5. Mutarotation. - and -forms of monosaccharides are readily interconverted when dissolved in water. This spontaneous process, called mutarotation, results in an equilibrium mixture of - and -furanose forms and - and -pyranose forms. The open chain that is formed during muterotation can participate in oxidation-reduction reactions

47. 6. Interaction with hydroxylamine
Aldoses with hydroxylamine forms oxymes.
This method use for obtaining lower aldoses from higher aldoses

48. 7. Intermolecular dehydratation
These reaction allow to distinguish hexoses from pentoses. Furfurol gives red color with aniline at the presence of HCl, 5-hydroxymethylfurfurol forms red color with resorcine (Selivanov reaction)

49. 8.Glycoside Formation. As you known, that hemiacetals and hemiketals can react with alcohols in acid solution to produce acetals and ketals. Because the cyclic forms of monosaccharides are hemiacetals and hemiketals, they react with alcohols to form acetals and ketals, as is illustrated for the reaction of -D-glucose with methyl alcohol.
The general name for monosaccharide acetals and ketals is glycoside. А glycoside is an acetal or а ketal fragment in а cyclic monosaccharide. More specifically, а glycoside produced from glucose is а glucoside, from galactose а galactoside, and so on. Glycosides, like the hemiacetals and hemiketals from which they are formed, can exist in both  and  forms. Glycosides are named by listing the alkyl or aryl group attached to the oxygen, followed by the name of the monosaccharide involved, with the suffix –ide appended to it.
-D-glucose Methyl -D-glucopyranoside
Methyl--D-
glucopyranoside
Methyl--D-
glucopyranoside

50. The acetal (or ketal) of a sugar is called a glycoside, and the bond between the anomeric carbon and the alkoxy oxygen is called a glycosidic bond.
Similar to the reaction of a monosaccharide with an alcohol is the reaction of a monosaccharide with an amine in the presence of a trace amount of acid. The product of the reaction is an N-glycoside. An N-glycoside has a nitrogen in place of the oxygen at the glycosidic linkage. An S-glycoside has a sulfur in place of the oxygen at the glycosidic linkage.

51. Ancarbohydrate part of the glycoside molecule called aglicone.
Glycosides very easy hydrolyses in acid medium:

52. O-, N- and S-glycosides

53. 9. Phosphate ester formation
9.Phosphate ester formation. The hydroxyl groups of а monosaccharide can react with inorganic oxyacids to form inorganic esters. Phosphate esters, formed from phosphoric acid and various monosaccharides, are commonly encountered in biological systems. For example, specific enzymes in the human body catalyze the esterification of the carbonyl group (carbon-1) and the primary alcohol group (carbon-6) in glucose to produce the compounds glucose 1-phosphate and glucose б-phosphate, respectively
These phosphate esters of glucose are stable in aqueous solution and play important roles in the metabolism of carbohydrates
-D-Glucose-1-phosphate
-D-Glucose-6-phosphate

54. 10. Amino Sugar Formation. Amino sugars of glucose, mannose, and galactose are common in nature. Such sugars are produced by replacing the hydroxyl group on carbon-2 on the monosaccharide with an amino group. Amino sugars and their N-acetyl derivatives are important building blocks of polysaccharides found in cartilage.
The N-acetyl derivatives of D-glucosamine and D-galactosamine are present in the biochemical markers on red blood cells, which distinguish the various blood types.
-D-Glucosamine -D-Glalactosamine N-acety1-D-glucosanune

55. 11. Acylation and alkylation of monosaccharides.
The OH-groups of monosaccharides show the chemistry typical of alcohols. For example, they react with acetyl chloride or acetic anhydride to form esters.
The OH-groups also react with dimethylsulfate/BaO or methyl iodide/silver oxide to form ethers. The OH group is a relatively poor nucleophile, so silver oxide or BaO is used to increase the leaving tendency of the iodide ion in the SN2 reaction.

56. 9. Isomerization. Monosaccharides undergo several types of isomerization, for example, after several hours an alkaline solution of D-glucose will also contain D- mannose and D- fructose. Both isomerizations involve an intramolecular shift of a hydrogen atom and a charge in the location of a double bond
The intermediate that is formed during this process is called an endiol. The reversible transformation of glucose to fructose is an example of an aldose-ketose interconversation. Because there is a change in the conversion of glucose to mannose is referred to as an epimerization. Several enzyme-catalyzed reactions involving endiols occur in carbohydrate metabolism.

57. Representatives of monosaccarides

58. Representatives of dezoxy- and aminosaccharides

59. Derivatives of monosacchrides
Ascorbinic acid – strong reduction agent.

60. Synthesis of ascorbic acid

61. Biologically important monosaccharides.
Of the many monosaccharides, the most important in the human body are the D-forms of glucose, galactose, fructose, and ribose. Glucose and galactose are aldohexoses, fructose is а ketohexose, and ribose is an aldopentose. All four of these monosaccharides are water-soluble, white, crystalline solids.
D-Glucose. Of all monosaccharides,
о-glucose is the most abundant in nature and the most important from а nutritional standpoint. Its Fischer projection.
D-Glucose
Ripe fruits, particularly ripe grapes (20% - 30% glucose by mass), are а good source of glucose, which is often referred to as grape sugar. Two other names for о-glucose are dextrose and blood sugar. The name dextrose draws attention to the fact that the optically active D-glucose, in aqueous solution, rotates plane-polarized light to the right. The term blood sugar draws attention to the fact that blood contains dissolved glucose. The concentration of glucose in human blood is fairly constant; it is in the range of mg per 100 mL of blood. Cells use this glucose as а primary energy source.
А 5% (m/v) glucose solution is often used in hospitals as an intravenous source of nourishment for patients who cannot take food by mouth. The body can use it as an energy source without digesting it.

62. D-Galactose. А comparison of the Fischer projections for D-galactose and D-glucose shows that these two compounds differ only in the configuration of the - ОН group and - Н group on carbon-4.
D-Galactose and D-glucose are epimers. D-Galactose is seldom encountered as а free monosaccharide. It is, however, а component of numerous important biochemical substances. In the human body, galactose is synthesized from glucose in the mammary glands for use in lactose (milk sugar), а disaccharide consisting of а glucose unit and а galactose unit. D-Galactose is sometimes called brain sugar because it is а component of glycoproteins (protein-carbohydrate compounds) found in brain and nerve tissue. D-Galactose is also present in the chemical markers that distinguish various types of blood - А, В, АВ, and O.
D-Galactose D-Glucose

63. D-Fructose is the most important ketohexose
D-Fructose is the most important ketohexose. It is also known as levulose and fruit sugar. Aqueous solutions of naturally occurring D-fructose rotate plane-polarized light to the left hence the name levulose. The sweetest-tasting of all sugars, D-fructose is found in many fruits and is present in honey in equal amounts with glucose. It is sometimes used as a dietary sugar, not because it has fewer calories per gram than other sugars but because less is needed for the same amount of sweetness. From the third to the sixth carbon, the structure of D-fructose is identical to that of D-glucose. Differences at carbons 1 and 2 are related to the presence of а ketone group in fructose and an aldehyde group in glucose.
D-Fructose D-Glucose

64. D-Ribose. The three monosaccharides previously discussed in this section have all been hexoses. D-Ribose is а pentose. If carbon-3 and its accompanying - Н and - ОН groups were eliminated from the structure of D-glucose, the remaining structure would be that of D-ribose
D-Ribose is а component of а variety of complex molecules, including ribonucleic acids (RNAs) and energy-rich compounds such as adenosine triphosphate (ATP). The compound 2-deoxy-D-ribose is also important in nucleic acid chemistry. This monosaccharide is а component of DNA molecules. The prefix deoxy- means "minus an oxygen"; the structures of ribose and 2-deoxyribose differ in that the latter compound lacks an oxygen atom at carbon-2.
D-Glucose
D-Ribose
D-Ribose
2-Deoxy-D-ribose

65. Thank you for attention !!!