Chemical Reactions of Carbohydrates Lecture 5 & 6 2024 PDF

Chemical Reactions of Carbohydrates Lecture 5 Dr. Moustafa Sarhan 1  Monosaccharides Monosaccharides are simple sugars in which there are one oxygen atom and two hydrogen atoms for each carbon atom present in the molecule. They have ge...

Chemical Reactions of Carbohydrates Lecture 5 Dr. Moustafa Sarhan 1  Monosaccharides Monosaccharides are simple sugars in which there are one oxygen atom and two hydrogen atoms for each carbon atom present in the molecule. They have general formula as (CH2O)n. Monosaccharides are reducing sugars. The test for reducing sugar is called Benedict’s test. They are sugars, which taste sweet. They are soluble in water and are insoluble in non-polar solvents. They exist in straight chains or in the ring or cyclic forms. They are classified according to the number of carbon atoms in each molecule as trioses (3C), tetroses (4C), pentoses (5C), hexoses (6C), heptoses (7) and so on. The names of all sugars end with -ose. Examples: Glyceraldehyde (triose), Erythrose (tetrose), Ribose (pentose), Glucose (hexose), Fructose (hexose), Galactose (hexose), Sedoheptulose (heptose), etc. They are used as a source of energy in respiration. They are important building blocks for large molecules. 1  Disaccharides Disaccharides are made up of two monosaccharides joined together by a condensation reaction. The condensation reaction is the joining of two molecules with the formation of a new chemical bond and a water molecule is released when the bond is formed. A glycosidic bond is formed between two monosaccharides. If carbon 1 on one monosaccharide joins to carbon 4 on another monosaccharide, it is called a 1,4-glycosidic bond. 2  Disaccharides Disaccharides are made up of two monosaccharides joined together by a condensation reaction. Examples: Maltose is formed from two α-glucose molecules joined together by a glycosidic bond. Sucrose is formed from a condensation reaction between a glucose molecule and a fructose molecule. Lactose is formed from glucose and a galactose molecule. Sucrose is a non-reducing sugar. Disaccharides can be split apart into two monosaccharides by breaking the glycosidic bond by adding water molecules, which is known as hydrolysis reaction. The water provides a hydroxyl group (-OH) and hydrogen (-H), which helps the glycosidic bond to break. Sucrose is the transport sugar and Lactose is the sugar found in milk which an important constituent of the diet of young mammals. 3  Chemical Reactions of Monosaccharides I. Oxidation of sugars (Sugar acids): - The product of oxidation depends on the nature of oxidizing reagent, a. Oxidation by weak oxidizing reagent: Example of oxidation Reagent: Bromine water, Type of Product: It oxidizes the first carbon and gives Aldonic acid. CH O CO OH Bromine water, O2 H C OH H C OH CH 2 OH CH 2 OH Glyceraldehyde Glyceric acid 4 Gluconic acid CH O CO OH H C OH H C OH HO C H brom ine w ater, O 2 HO C H H C OH H C OH H C OH H C OH CH 2 OH CH 2 OH D-G lucose D-G luconic acid Gluconic acid is an intermediate in carbohydrate metabolism and used as Ca2+ gluconate for intravenous supplementation of calcium for slow dissociation. B. Oxidation by moderate oxidizing reagents : Oxidizing Reagent: H2O2 (hydrogen peroxide) or diluted HNO3 Type of Product: They oxidize the last carbon (CH2OH) to give uronic Acids. Examples: Glucuronic acid: It is synthesized in the liver. 5  CH O CH O H C OH H C OH HO C H H2O 2 HO C H H C OH Dil. Nitric acid H C OH H C OH H C OH CH 2 OH CO OH D-Glucose D-Glucuronic acid Importance of glucuronic acid: 1- Glucuronic acid enters in the structure of very important molecules such as mucopoly- saccharides. 2- It is used for excretion of bilirubin and steroid hormones and detoxication of certain drugs and several toxins by conjugation. 6 C. Oxidation by strong oxidizing reagent: Oxidizing Reagent: Concentrated HNO3 Type of Product: It oxidizes the first and last carbon to give aldaric acid. CH O CO OH H C OH H C OH HO C H HO C H This reaction is important O2 H C OH H C OH to differentiate between Conc. Nitric acid H C OH H C OH glucose and galactose since CH 2 OH CO OH glucaric acid is water D-Glucose D-Glucaric acid soluble, whereas, mucic CH O CO OH acid is insoluble in water H C OH H C OH HO C H O2 HO C H HO C H Conc. Nitric acid HO C H H C OH H C OH CH 2 OH CO OH D-Galactose D-Galactaric acid Mucic acid 7 II. Reduction of monosaccharides (sugar alcohols): - Reduction of monosaccharides gives sugar alcohols. Examples: 1- Reduction of Glyceraldehyde gives glycerol that enters in structure of lipids. CH O CH 2 OH H2 H C OH H C OH Na ama lgum, H 2 SO 4 CH 2 OH CH 2 OH Glyceraldehyde Glycerol 2- Reduction of Ribose gives Ribitol that is a part of the structure of vitamin B2 (Riboflavin). CH O CH 2 OH H C OH H C OH H2 H C OH H C OH H C OH Na a ma lgum, H 2 SO 4 H C OH CH 2 OH CH 2 OH Ribose Ribitol 8 3- Reduction of glucose gives sorbitol or glucitol that enters in medical industries CH O CH 2 OH H C OH H C OH HO C H H2 HO C H H C OH H C OH Na ama lgum, H 2 SO 4 H C OH H C OH CH 2 OH CH 2 OH Glucose Sorbitol 4- Mannose: Gives Mannitol Mannitol: is a Diuretic….it is injected intravenously to reduce intracranial pressure in cases of meningitis, cerebral hemorrhage or thrombosis and is used in kidney function testing CH O CH 2 OH HO C H HO C H HO C H H2 HO C H H C OH H C OH Na ama lgum, H 2 SO 4 H C OH H C OH CH 2 OH CH 2 OH Mannose Mannitol 9 III. Effect of acids on sugars: Phosphoric acid (H3PO4): It reacts with sugars to form very important phosphate esters, such as glucose-6- phosphate, 10 III. Effect of acids on sugars: Nitric acid: Diluted nitric acid gives uronic acids while concentrated nitric acid gives aldaric Acids. Conc. HCl or H2SO4: These are strong dehydrating reagents that remove three molecules of water producing cyclic unsaturated aldehyde. IV. Effect of alkalis on monosaccharides: Concentrated alkalis like NaOH: on heating breaks down the sugar Diluted alkalis at low temperature causes: - Stimulation of mutarotation - Transformation of glucose into a mixture of glucose, fructose and mannose. 11 V. Reducing properties of monosaccharides Monosaccharides reduce the following reagents: 1-Cupric hydroxide [Cu (OH)2) in case of Fehling’s or Benedict reagents. 2-Bismuth Silver. 3-Picric acid. VI. Fermentation of sugars - Definition : Certain sugars by several biochemical steps can produce ethyl alcohol and carbon dioxide. -Examples: Polysaccharides are non-fermentable. Glucose, mannose and fructose are fermentable, whereas, galactose is weakly fermented. Sucrose and maltose are fermentable. Pentoses are non-fermentable. Lactose is non-fermentable due to absence of lactase enzyme from yeast. 12  Chemical Reactions Related to Color Tests of Carbohydrates 1) Molisch’s test:  Any carbohydrate + Alcoholic (-naphthol )then add conc. H2SO4 on the wall of the test tube form Violet ring between the two layers. H2SO4 Violet ring 13  Chemical Reactions Related to Color Tests of Carbohydrates 2) Effect of conc. acids: Treatment with conc. mineral acid (HCl or H2SO4) leads to dehydration of sugars and formation of the corresponding furfural. Dehydration Furfural Pentoses (volatile) O CHO Dehydration Hexoses 5-Hydroxymethyl HOH 2 C O CHO furfural (less volatile) 14  Chemical Reactions Related to Color Tests of Carbohydrates  Reaction of furfural with amines resulted in Schiff’s bases with different colors used as color tests.  3) Furfural test : Differentiate between Pentoses (Fructose) and Hexoses (Glucose):  Pentose + conc. acid + heat expose the vapours to Red colour Aniline acetate paper  Hexoses give negative result. 15 Chemical Reactions Related to Color Tests of Carbohydrates Resorcinol test (for keto-hexoses): Sugar few crystals Equal volume Rose Red solution + of Resorcinol + of conc. HCl Colour warm on water bath 16 5) Ozazone Test:  Sugar (H2O)+ phenyl hydrazine HCl+ NaAc, heat (50 min), cool examine ozazone crystals under the microscope. The ozazone are yellow, crystalline with sharp m.p. Glucose, mannose fructose will give the same crystals (reaction involves C-1 and C-2) due to destruction of asymmetric center at C-2. CHO CH=N-NH-Ph 3 PhNH-NH 2 CHOH phenyl hydrazine HCl CH=N-NH-Ph + Ph-NH 2 + NH 3 sugar Ozazone crystals (characteristic) 17 6) Effect of Alkalis  Strong alkalis: Polymerization Weak alkalis: Isomerization e.g. H C=O CHOH CH 2 OH CH OH C OH C=O HO CH HO CH HO CH CH OH CH OH CH OH CH OH CH OH CH OH CH 2 OH CH 2 OH CH 2 OH D-Glucose intermediate D-Fructose CHO HO CH HO CH CH OH CH OH CH 2 OH D- Mannose 18  7) Oxidation:  a) Mild Oxidation:  These are oxidizing agents like Bromine water (or I2) that convert the CHO group to COOH to produce “onic acids”.  Colour tests based on this reaction:  Fehling’s reduction test: Fehling’s B Heat on water Sugar + Fehling’s A + (NaOH and Na,K bath Red tartarate, solutions (CuSO4) Rochell salt) Precipitate RCHO + Cu++ RCOOH + Cu2O (ppt cuprous oxide) CHO COOH CH OH CH OH I2 or Fehling's HO CH HO CH CH OH CH OH CH OH CH OH CH 2 OH CH 2 OH D-Glucose Gluconic acid 19   Barfoed’s test: Used to distinguish monosaccharides from disaccharides as Monosaccharides give a cuprous oxide precipitate in dilute acid more quickly than the disaccharides. Barfoed’s Red ppt reagent with Sugar (Cu solution Acetate/Acetic Heat for 3 minutes monosacch +. on boiling water arides only acid) bath *Acidic medium decreases the oxidation power of Cu++. 20 Sugar derivatives and disaccharides Lecture 6 Dr. Moustafa Sarhan  Sugar Derivatives 1. Amino sugars or sugar amines. 2. Deoxy sugars. 3. Sugar acids (product of oxidation of sugars). 4. Sugar alcohols (product of reduction of sugars). 5. Glycosides 1- Amino sugars (sugaramines): Definition: Replacing OH group on C2 by an amino group (NH2) and it can be acetylated and sulfated. Examples: 1- Glucosamine 2- Galactosamin 3- Mannosamin 4- Sialic acid 1 1- Glucosamine: Glucosamine is also called chitosamine because it is the only sugar derivative in chitin. Structure: CH OH 2 CH OH 6 CH O-SO H2 2 3 O O O H H H H H H H H H H OH H H OH OH 2 OH OH 2 OH 2 OH OH OH H NH 2 H HN C CH 3 H NH-SO 3 H O -D-glucoamine N-acetyl-glucosamine sulfated glucosamine Importance: - Enters in the structure of exoskeleton of insects (chitin, so it is called chitosamine). - Enters in the structure of mucopolysaccharides, hyaluronic acid contain N-acetyl glucosamine and heparin contain sulfated glucosamine. 2 2- Galactosamine (Chondrosamine): the major sugar derivative in (chondroitin sulfate), it may be acetylated or sulfated, Structure: 6 CH 2 OH CH 2 OH CH 2 O - SO 3 H O O O-SO 3 H O OH H OH H H H H H 4 H OH H OH H OH 2 OH H 2 OH H 2 OH H H NH 2 H HN C CH 3 H HN C CH 3 O O - D-galactosamine N- acetyl-galactosamine sulfated N-acetyl- galactosamine Importance: It enters in the structure of the sulfate-containing mucopolysaccharides (chondroitin sulfate) and glycolipids. 3- Mannosamine: CH 2 OH Structure: H O H H NH 2 OH 2 OH OH H H  -D-Mannosam ine Importance: Importance: Mannosamine enters in the structure of antibiotics, e.g., erythromycin together with other amino sugars where they are required for the activity of these antibiotics. 3 4- Sialic acid: - It is an amino sugar since it contains NH2 group, It is a sugar acid since it contains COOH group and a deoxy sugar since it contains two hydrogen atoms at C3. Structure: O NH- C-CH 3 H O COO H H OH H OH CH 2 O H H OH H H OH H Sialic acid Importance: - It enters in structure of glycoproteins and glycolipids, e.g., gangliosides. 4  2. Deoxysugars: Definition: These are sugars in which OH group is replaced by H. At C2 gives Deoxy sugar proper, e.g., deoxyribose that enters in structure of DNA., 5  2. Deoxysugars: At C6 gives methyl pentoses (Methylose), e.g., L-galactose gives L-fucose and, L-Mannose gives L-rhamnose. L-rhamnose and L-fucose enter in the structure of glycoproteins, e.g., blood group substance. CHO CHO CHO CHO HO C H HO C H H C OH H C OH H C OH H C OH H C OH H C OH H C OH H C OH HO C H HO C H HO C H HO C H HO C H HO C H CH 2 OH CH 3 CH 2 OH CH 3 L-galactose L-fucose L-Mannose L-Rhamnose 6 3- Glycosides Definition: They are products of the reaction of the OH group of the anomeric carbon with either another OH group or NH2 group from another compound. The other compounds may be another sugar, called glycan or a non- sugar, called aglycan. The glycosides can be named according to the type of sugar, e.g., glucose forms glucosides …etc. Types of Glycosides: A. Glycosides containing R–O–R (ether linkage): e.g. Disaccharides: e.g., lactose and maltose B. R-N-R Glycosides: e.g. Nucleotides: The sugar is ribose or deoxyribose linked with purine and pyrimidine bases and Glycoproteins. 7  CH 2 OH CH 2 OH O O H H OH..... H H H H 1 4 Disaccharides: OH H O OH H H..... OH OH H OH H OH -Glucose Glucose and  Maltose Nucleotides: 8  Disaccharides A- Reducing Disaccharides: 1- Maltose (malt sugar): Structure and Properties: It has a free aldehyde group (anomeric carbon), therefore it: - exists in  and  forms. - exhibits mutarotation. - is a reducing disaccharide. - gives osazone called - maltosazone (Rosette shaped). - It is a fermentable sugar, due to -glucosidic bond. - It is produced during digestion of starch. - It is hydrolyzed by acids and in human intestine by maltase enzyme to give 2 molecules of glucose. 9 2-Lactose (Milk Sugar): Structure and Properties: -It is the milk sugar with free aldehyde making it is having  and -forms. - It is digestible by lactase into glucose and galactose. -It is excreted in urine of pregnant and lactating females and can be distinguished from glucose by: 1. - Osazone test. 2. - Bradford's test. 3. -Polariscope (each has its specific rotation)… …....there are more methods 10  B. Non-reducing Disaccharides: CH 2 OH 1- Sucrose: H O H H -Glucose 1 OH H OH H OH Structure and Properties: CH 2 OH O O  -Fructose - It is table sugar and sugar of cane H H OH 2 CH 2 OH - It is a fermentable sugar. OH H Sucrose The 2 anomeric carbons (C1 of glucose and C2 of fructose) are involved in the linkage, therefore it is: - Non-reducing sugar. - Non osazone forming. - Not mutarotating. - Not having  or -forms. 11  Invert Sugar Definition: It is the product of sucrose hydrolysis by sucrase enzyme (Invertase) or by acid hydrolysis (HCl) containing equimolar mixture of Glucose and fructose sugars. Why it is named invert Sugar????? Because the optical activity of sucrose before hydrolysis is d but when it is hydrolyzed, the product of hydrolysis become l Why??????? This is because the levorotatory power of fructose (-92.5) cancels the dextrorotatory power of glucose (+52.5) since they are at equal proportions in the product. - This is why this sugar is called invert sugar. Sucrose enzyme is therefore, also called invertase enzyme. 12  Comparison between sucrose and invert sugar Item Sucrose Invert sugar Formed of: -glucose and - An equimolar mixture of Structure fructose linked by 1,2- free -glucose and - linkage. fructose. Optical activity: Dextrorotatory. Levorotatory. Non-reducing (no free CHO Reducing (there are free Reductive ability: or C=O groups). CHO and C=O groups) Gives needle-shaped Osazone: Does not form osazone. crystals. Digestion: Needs digestion (sucrase). No further digestion. Bees honey and invert Other names: Cane and table sugar. sugar. 13  Some Monosaccharide derivatives in Pharmacy 1) Gluconic acid and its salts: Preparation:  Gluconic acid is prepared from glucose by mild oxidation using either dilute HNO3 or Br2/Na2CO3 or Electrically or by fermentation using Acetobacter aceti. Uses:  Ca gluconate is used (by i.v. or orally) for treatment calcium deficiency.  Ferrous gluconate, (orally or by i.v.) is used in iron deficiency.  These salts are characterized by being more easily absorbed than other Ca or Fe salts. 14  2) Glucuronic Acid: Naturally present in Gums and Mucilage's. It can be prepared by Enzymatic oxidation of glucose. Uses: Treatment of certain arthritic condition as it is a component of cartilages, joint capsules and fluids, nerve sheath and tendons. 3)Aurothioglucose:  Also known as gold thioglucose, water soluble Treatment of rheumatic arthritis by IM injection.  Not uniformly effective. CH 2 OH O H H H OH H S Au OH H OH Aurothioglucose 15 Auranofin: It is the alkyl Phosphine Gold complex with Acetylated thioglucose. Treatment of rheumatic arthritis orally. CH 2 OR O S Au P(C 2 H 5 ) 3 H H OR H H OR R= COCH 3 H OR Auranofin 16 4) Sorbitol and Mannitol: sugar alcohols Preparation: Sorbitol is prepared by reduction of glucose and mannitol by reduction of mannose. Uses: Sorbitol is used as sweetening agent in dietetic food (not absorbed), chewing gum&tooth pastes. Test of kidney function (iv), not metabolized. Mannitol is used as an osmotic diuretic, laxative, and in tests of kidney function (not metabolized if i.v.), vasodilator (mannitol hexanitrate), 17  5) Glucosamine Source: strong acid hydrolysis of chitin (shells of crustaceae) Uses : regeneration of cartilage (as sulphate salt) in joint injuries and arthritis CH2OH O OH H H OH H H OH H NH2 18 6) Ascorbic acid  Preparation:  -extraction from citrus fruits  - synthesis from glucose  Uses:  -Cure its deficiency (scurvy), cold, capillary fragility  -Antioxidant in some pharmaceutical preparations CH2OH HOHC O O OH HO ٤١ Vitamin C 19 Next………… polysaccharides ٤٢