Lecture 8-9 Carbohydrates Medicine PDF

BIOMOLECULES – CARBOHYDRATES Part I – MONOSACCHARIDES Part II – DI- and POLYSACCHARIDES DR. KHATUNA BARBAKADZE Learning Objectives:  Monosaccharides - Classification  Constitutional Isomers  Stereoisomers: D/L-Sugars, Epimers, Diastereomers  Cyclic Hemiacetals &...

BIOMOLECULES – CARBOHYDRATES Part I – MONOSACCHARIDES Part II – DI- and POLYSACCHARIDES DR. KHATUNA BARBAKADZE Learning Objectives:  Monosaccharides - Classification  Constitutional Isomers  Stereoisomers: D/L-Sugars, Epimers, Diastereomers  Cyclic Hemiacetals & Hemiketals  Anomeric Carbon; Mutarotation  Conformations of Pyranoses  Reducing / Nonreducing Sugars  Chemical Properties  Di- & Polysaccharides INTRODUCTION  Named so because many have formula Cn(H2O)n, (n≥3) Produced from CO2 and H2O via photosynthesis in plants: Range from as small as glyceraldehyde (Mw = 90 g/mol) to as large as amylopectin (Mw > 200,000,000 g/mol) Carbohydrates are polyhydroxyaldehydes, polyhydroxyketones, or substances that give such compounds on hydrolysis  Carbohydrates are usually classified according to their structure as Monosaccharides, Disaccharides, Oligosaccharides, or Polysaccharides  Monosaccharides - simple sugars with multiple OH groups.  Disaccharides - 2 monosaccharides covalently linked.  Oligosaccharides - 3 to 10 monosaccharides covalently linked. (oligos is Greek for “few”)  Polysaccharides - polymers consisting of chains of monosaccharide or disaccharide units.  Based on number of carbons (3, 4, 5, 6), a Monosaccharide is a triose, tetrose, pentose or hexose Basic nomenclature: – number of carbon atoms in the carbohydrate + -ose – example: three carbons = triose Common functional groups - Isomerism: – All carbohydrates initially had a carbonyl functional group – aldose is a carbohydrate with aldehyde functionality – ketose is a carbohydrate with ketone functionality  Reading the Names Aldohexose: sugar contains 6 carbons and is aldehyde Ketohexose: sugar contains 6 carbons and is ketone Aldopentose: sugar contains 5 carbons and is aldehyde Ketopentose: sugar contains 5 carbons and is ketone Constitutional Isomerism  The senior substituent here is the Chiral Centers in Glucose carbonyl group, therefore numbering starts there Among the moieties of glucose, we see: – 1 carbonyl – 5 hydroxy groups of these hydroxy groups, there are 4 –CHOH and 1 –CH2OH The carbonyl carbon is in sp2, therefore it cannot contribute to tetrahedral chirality Hydroxymethyl (–CH2OH) contains two identical substituents (hydrogens), therefore it is symmetric and achiral The –CHOH groups are chiral as all 4 substituents there are different (2R,3S,4R,5R)-2,3,4,5,6- pentahydroxyhexanal Chiral Centers in Fructose Among the moieties of fructose, we see: – 1 carbonyl – 5 hydroxy groups of these hydroxy groups, there are 3 –CHOH and 2 –CH2OH The carbonyl carbon is in sp2, therefore it cannot contribute to tetrahedral chirality Hydroxymethyl (–CH2OH) contains two identical substituents (hydrogens), therefore it is symmetric and achiral The –CHOH groups are chiral as all four substituents there are different (3S,4R,5R)-1,3,4,5,6- Pentahydroxyhexan-2-one Chirality of Monosaccharides D- (dextrorotatory) & L-(levorotatory) saccharides Glyceraldehyde serves as a “template” structure Note the position of –OH groups  D and L isomers of a sugar are enantiomers.  Most hexoses in living organisms are D-stereoisomers.  If the stereogenic carbon farthest from the aldehyde or ketone group had the same configuration as D-glyceraldehyde (hydroxyl on the right), the compound was called a D-sugar.  If the configuration at the remote carbon had the same configuration as L-glyceraldehyde (hydroxyl on the left), the compound was an L-sugar. Illustration Epimers Epimers are NOT mirror images, and therefore are NOT enantiomers. Epimers are diastereomers; diastereomers have different physical properties Epimers of Aldoses Epimers of Ketoses Enantiomers enantiomers By convention, we arrive at L-aldose ONLY if we invert configurations of ALL chiral centers  Aldehyde and ketone carbons are electrophilic. Alcohol oxygen atom is nucleophilic. When aldehydes are attacked by alcohols, hemiacetals form. When ketones are attacked by alcohols, hemiketals form. These reactions form the basis of cyclization of sugars. Cyclic Structures are most Adequate  The nucleophilic alcohol attacks the electrophilic carbonyl carbon, allowing formation of a hemiacetal. As a result, the linear carbohydrate forms a ring structure. At the completion of this structure, the carbonyl carbon is reduced to an alcohol. The orientation of the alcohol around the carbon is variable and transient. Pyranosic Forms of Aldohexoses β-D-Glucose is the most stable of all the aldohexoses, so we should not be surprised that it is the most prevalent aldohexose in nature Furanosic Forms of Aldohexoses Pyranosic forms of aldohexoses are preferable  Furanosic Forms of Ketohexoses Furanosic forms of ketohexoses are customary Reactions of Monosaccharides Aldoses can be distinguished from ketoses by observing what happens to the color of an aqueous solution of Br2 when it is added to the sugar. Br2 is a mild oxidizing agent and easily oxidizes the aldehyde group, but it cannot oxidize ketones or alcohols.  Both aldoses and ketoses are oxidized to aldolic acids by Tollens reagent (Ag+, NH3, HO−), so Tollens reagent cannot be used to distinguish them.  Tollens reagent only oxidizes aldehydes, but since the oxidation reaction is carried out in a basic solution, a ketose is converted into an aldose by an enediol rearrangement, and the aldose is then oxidized by Tollens reagent:  Other mild oxidizing agents:  Fehling’s reagent (Cu2+ complexed with tartrate ion)  Benedict’s reagent (Cu2+ complexed with citrate ion) Acylation – Formation of Esters ALKYLATION (Etherification) - Conversion to Ethers  The preference of certain substituents bonded to the anomeric carbon for the axial position is called the anomeric effect. stabilization of the molecule - substituent is axial: substituent is equatorial - neither of electron delocalization from the sp3 orbital the orbitals that contain a lone pair of oxygen into the σ* antibonding orbital is aligned correctly for overlap of the C–Z bond An Equilibrium Mixture of Maltose Isomers Gentobiose is one of the product that form when glucose is caramelized by heating, thus tempering the sweetness of the sugar mass with its distinctive bitter note. Polysaccharides are large molecules of monosaccharides that are connected to each other through their anomeric carbons. There are two types of polysaccharides: 1. Storage polysaccharides contain only α-glucose units. Three important ones are starch, glycogen, and amylopectin. 2. Structural polysaccharides contain only -glucose units. Two important ones are cellulose and chitin. Chitin contains a modified -glucose unit. Storage Polysaccharides Amylose and Amylopectin — Starch Starch is a mixture of amylose and amylopectin and is found in plant foods. Amylose makes up 20% of plant starch and is made up of 50–300 D-glucose units bonded α(1→4) in a continuous chain. Long chains of amylose tend to coil. Amylopectin makes up 80% of plant starch and is made up of 300-5000 D-glucose units connected by α(1→4) glycosidic bonds. About every 25 glucose units of amylopectin, a branch of glucose units are connected to the glucose by an α(1→6) glycosidic bond. Glycogen Glycogen is a storage polysaccharide found in animals. Glycogen is stored in the liver and muscles. Its structure is identical to amylopectin, except that α(1→6) branching occurs about every 12 glucose units. When glucose is needed, glycogen is hydrolyzed in the liver to glucose. Structural Polysaccharides Cellulose Cellulose contains glucose units bonded (1→4). This glycosidic bond configuration changes the three-dimensional shape of cellulose compared with that of amylose. The chain of glucose units is straight. This allows chains to align next to each other to form a strong rigid structure.