Week 2 Lectures Cyclic Structure Common Monosaccharides Important Reactions and derivatives Common Monosaccharides

Hemiacetals & Hemiketals Formation An aldehyde or a ketone can react with an alcohol in a 1:1 ratio to yield a hemiacetal or hemiketal, respectively, creating a new chiral center at the carbonyl carbon

Cyclic Structure Monosaccharides exists in solution as ring structures in which the carbonyl (aldehyde or ketone) group reacts with a hydroxyl group in the same molecule forming a ring. They form either: six-membered rings (pyranose) or five-membered ring (furanose).

Cyclization of the open-chain form of sugar Glucose forms an intra-molecular hemiacetal hemiacetal, as the C1 aldehyde & C5 OH react, to form a 6- member pyranose ring. (Fisher projection) (Haworth projection) Fructose forms an intra-molecular hemiketal hemiketal, as the C2 Ketone & C5 OH react, to form a 5- member furanose ring.

Haworth's projections = cyclic structure Cyclization of glucose produces a new asymmetric center at C1. The 2 stereoisomers are called anomers, α & β. α (OH below the ring) β (OH above the ring). Anomeric carbon 6CH2OH 6CH2OH 5 O 5 O H H H OH H H 4 1 OH H 1 4 OH H OH OH OH H 3 2 3 2 H OH H OH α-D-glucose β-D-glucose

Anomers are the stereoisomers (α and β) O O OH α-D-Glucose β-D-Glucose CH2OH CH2OH O O OH OH OH OH OH OH OH OH α-D-Glucose β-D-Glucose CH2OH C O CH2OH CH2OH CH2OH OH HO C H HCOH O O OH OH OH CH2OH H C OH OH OH CH2OH α-D-Fructose β-D-Fructose D-Fructose

Home work

1) α-D glucopyranose 2) β -D mannopyranose 3) α-D fructofuranose • Write the chemical structure of the following molecules: 1) α-D glucopyranose 2) β -D mannopyranose 3) α-D fructofuranose 4) β -L galactopyranose

Common Monosaccharides

Common Monosaccharides 1. Glucose 2. Galactose 3. Fructose 4. Ribose and deoxyribose

D-Glucose An aldohexose with the formula C 6H12O6. It is the most abundant monosaccharide. also called dextrose. Known as blood sugar in the body (found in the blood stream and in tissue fluids). provides energy for cells when it is metabolized.. (C6H12O6 + 6O2 6CO2 + 6H2O + Energy). It requires no digestion and can be given intravenously to patients unable to take food by mouth. Excess glucose is converted to the polysaccharide glycogen or fat. Found in fruits, corn syrup, and honey.

Blood Glucose Level In the body, glucose has a normal concentration of 70-110 mg/dL. Insulin, regulates blood glucose levels. When glucose concentration increases after eating, insulin stimulates the uptake of glucose in tissues and its conversion to glycogen. In a glucose tolerance test, blood glucose is measured for several hours after ingesting glucose.

D-Galactose It is not found free in nature. CHO H C OH HO CH HOC H It is not found free in nature. It is obtained from lactose (The milk sugar). H C OH Galactose is present in some glycoproteins and glycolipids It is important in cellular membranes. CH2OH D-Galactose It is converted to glucose in the liver by an enzyme called an epimerase (galactose is an epimer of glucose). Galactosemia is a rare inherited disease that results in infants being unable to metabolize galactose because of a deficiency of an enzyme needed to metabolize galactose. In galactosemia, galactose accumulates causing a variety of physical problems, including cataracts, cirrhosis, and mental retardation. The patient should avoid all milk products with lactose.

D-Fructose It is a ketohexose C CH2OH D-Fructose C O HO C H HCOH H C OH CH2OH It is a ketohexose C 6H12O6. D-Fructose It is the most soluble and sweetest sugar (approximately twice as sweet as glucose) It is the sugar of fruits, honey and semen. Converts to glucose in the body by an enzyme called isomerase. Fructosemia is fructose intolerance. infants that suffer from this disease show vomiting and severe malnutrition

Ribose and deoxyribose Ribose and deoxyribose are aldopentoses They are often incorporated into larger biomolecules: o DNA and RNA (nucleic acids) o NADPH(reducing agent) o NAD+ (oxidizing agent)

Important reactions of monosaccharides and Monosaccharide derivatives

Important reactions of monosaccharides Reduction Glycosides formation Oxidation Esters formation

Carbonyl group Hydroxyl group Sugars Alditols Glucose Reduction Either done catalytically (hydrogen and a catalyst) or enzymatically The resultant product is a polyol or sugar alcohol (alditol) Carbonyl group Reduced to Hydroxyl group Sugars Alditols Reduced to (polyhydroxy aldehydes or ketones) (polyhydroxy alcohols) -CHO -CH2OH NaBH4 Glucose Glucitol (Sorbitol)

The reduction of a keto-sugar produces two Fructose NaBH4 Glucitol + Mannitol + NaBH4 The reduction of a keto-sugar produces two different isomers of alditols (why?)

Important examples of sugar alcohols Sorbitol (glucitol), derived from glucose, is used as a sweetener. Glycerol, derived from Glyceraldehyde & Dihydroxyacetone, is present in the structure of many lipids (neutral fats and phospholipids). Ribitol, from ribose, is present in FAD (oxidizing agent), and in the structure of riboflavin (Vitamin B2) Myo-Inositol: It is one of the isomers of inositol, which is a hydroxylated cyclohexane. It is present in the structure of a phospholipid. (Cell membrane).

Sugars Sugar Acids Oxidation Oxidation of sugars produces Sugar acids The type of sugar acids that are produced depends on the oxidizing agent

1 CHO 6 CH2OH 1 COOH 1 COOH 6 COOH 6 COOH Sugar Acids Aldose Vigorous Oxidation Oxidation at C1 & C6 1 COOH 1 COOH CHO CH2OH 6 COOH 6 COOH Aldaric Acid Uronic Acid Aldonic Acid -ose -onic -ose -aric -ose -uronic

Sugar Acids CHO CH2OH HNO350% / Heat COOH COOH CHO CH2OH COOH COOH Glucose HNO350% / Heat COOH COOH CHO CH2OH COOH COOH Glucaric Glucuronic Gluconic

Important examples of sugar acids D-Gluconic acid and D-glucuronic acid, are carboxylic acid sugars present in many oligosaccharides and polysaccharides. Glucuronic acid is used in detoxification reactions. The conjugation between it and toxic compounds makes them more soluble before excretion. L-Ascorbic acid (Vitamin C), formed in plants and some animals(not human) from glucose, is considered as sugar acid.

Esters formation The hydroxyl groups of sugars can react with acids and derivatives of acids to form esters. The phosphate esters are particularly important ones because they play an important role in the metabolism of sugars. Phosphate esters are formed by transfer of a phosphate group from ATP (adenosine triphosphate) to give the phosphorylated sugar and ADP (adenosine diphosphate)

The newly formed bond is called a glycosidic bond. Glycosides formation The hydroxyl group (-OH) of the anomeric carbon of a sugar can react with another hydroxyl group(R’OH) to form a glycoside. The newly formed bond is called a glycosidic bond. Glycosidic bonds between monosaccharide units are the basis for the formation of oligosaccharides and polysaccharides. glycosidic bond + CH3OH HO H2O α-D Glucose Methyl α-D Glucoside

Monosaccharide Derivatives Important Monosaccharide Derivatives A number of monosaccharide derivatives appear in nature, and many are incorporated into oligo- and polysaccharides. The four major classes of monosaccharide derivatives are: deoxy sugars, amino sugars, sugar alcohols, and sugar acids.

Deoxy Sugars • one of the hydroxyl groups of the sugar is substituted by hydrogen atom substituted by -OH -H The sugar component of RNA’s backbone The sugar component of DNA’s backbone

Deoxy Sugars substituted by -OH -H Gal CH2OH 6-deoxy β-L Galactose β-L Fucose β-L Galactose β-L Fucose is an important component of some cell membrane glycoproteins and blood group antigens

Amino Sugars • one of the hydroxyl groups of the sugar is substituted by an Amino group (—NH2) or one of its derivatives substituted by -OH -NH2 Glu NH2 2-amino β-D Glucose β -D Glucosamine β-D Glucose

-OH -NH-CO-CH3 Glu Amino Sugars substituted by N-acetyl amino group β-D Glucose N-acetyl β -D Glucosamine components of bacterial cell walls and the building block of chitin

Important examples of Amino sugars are important constituents of mucopolysaccharides (GAGs) and some types of glycolipids e.g. gangliosides. They are conjugated with acetic acid and/or sulfate to form different derivatives such as: Glucosamine-2,6 bisulfate presents in heparin. N-acetyl-galactosamine (Gal Nac) 4 or 6-sulfate presents in chondroitin sulfate. Sialic acid or N-acetyl-neuraminic acid (NANA): It enters in the structure of many glycolipids and glycoproteins (structure of cell membranes) and has many important functions in: cell recognition and interaction. cell membrane receptors. cell membrane transport systems.