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Download Chapter 25. Biomolecules: Carbohydrates
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Chapter 25. Biomolecules: Carbohydrates Based on McMurry’s Organic Chemistry, 6th edition ©2003 Ronald Kluger Department of Chemistry University of Toronto Importance of Carbohydrates Distributed widely in nature Key intermediates of metabolism (sugars) Structural components of plants (cellulose) Central to materials of industrial products: paper, lumber, fibers Key component of food sources: sugars, flour, vegetable fiber Contain OH groups on most carbons in linear chains or in rings Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 2 Chemical Formula and Name Carbohydrates have roughly as many O’s as C’s (highly oxidized) Since H’s are about connected to each H and O the empirical formulas are roughly (C(H2O))n Appears to be “carbon hydrate” from formula Current terminology: natural materials that contain many hydroxyls and other oxygen-containing groups Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 3 Sources Glucose is produced in plants through photosynthesis from CO2 and H2O Glucose is converted in plants to other small sugars and polymers (cellulose, starch) Dietary carbohydrates provide the major source of energy required by organisms Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 4 25.1 Classification of Carbohydrates Simple sugars (monosaccharides) can't be converted into smaller sugars by hydrolysis. Carbohydrates are made of two or more simple sugars connected as acetals (aldehyde and alcohol), oligosaccharides and polysaccharides Sucrose (table sugar): disaccharide from two monosaccharides (glucose linked to fructose), Cellulose is a polysaccharide of several thousand glucose units connected by acetal linkages (aldehyde and alcohol) A disaccharide derived from cellulose Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 5 Aldoses and Ketoses aldo- and keto- prefixes identify the nature of the carbonyl group -ose suffix designates a carbohydrate Number of C’s in the monosaccharide indicated by root (-tri-, tetr-, pent-, hex-) Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 6 25.2 Depicting Carbohydrate Stereochemistry: Fischer Projections Carbohydrates have multiple chirality centers and common sets of atoms A chirality center C is projected into the plane of the paper and other groups are horizontal or vertical lines Groups forward from paper are always in horizontal line. The oxidized end of the molecule is always higher on the page (“up”) The “projection” can be seen with molecular models Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 7 Stereochemical Reference The reference compounds are the two enantiomers of glyceraldehyde, C3H6O3 A compound is “D” if the hydroxyl group at the chirality center farthest from the oxidized end of the sugar is on the right or “L” if it is on the left. D-glyceraldehyde is (R)-2,3-dihydroxypropanal L-glyceraldehyde is (S)-2,3-dihydroxypropanal Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 8 The D-Sugar Family Correlation is always with D- (+)-glyceraldehyde (R) in C-I-P sense Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 9 Rosanoff Structural Families The structures show how the “D” and “L” family members are identified by projection of the bottom chirality center The rest of the structure is designated in the name of the compound The convention is still widely used Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 10 Working With Fischer Projections If groups are not in corresponding positions, they can be exchanged three at a time in rotation – work with molecular models to see how this is done The entire structure may only be rotated by 180 While R, S designations can be deduced from Fischer projections (with practice), it is best to make molecular models from the projected structure and work with the model Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 11 25.3 D, L Sugars Glyceraldehyde exists as two enantiomers, first identified by their opposite rotation of plane polarized light Naturally occurring glyceraldehyde rotates planepolarized light in a clockwise direction, denoted (+) and is designated “(+)-glyceraldehyde” The enantiomer gives the opposite rotation and has a (-) or “l” (levorotatory) prefix The direction of rotation of light does not correlate to any structural feature Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 12 IUPAC Definitions1996 Fischer-Rosanoff Convention - according to which (+)- glyceraldehyde, now known to be (R)-2,3-dihydroxypropanal, was named D-glyceraldehyde (with the enantiomer Lglyceraldehyde and its racemate DL-glyceraldehyde) and taken to have the absolute configuration represented by the Fischer projection formula shown below. The atom numbered 1 according to normal nomenclature rules is conventionally placed at the top of the main chain, which is drawn vertically and other groups are drawn on either side of that main chain. The convention is still in use for -amino acids and for sugars IUPAC, Commission on Nomenclature of Organic Chemistry, Section E: Stereochemistry (Recommendations 1974), Pure Appl. Chem. 45, 11-30 (1976) D-glyceraldehyde L-glyceraldehyde Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 13 25.4 Configurations of the Aldoses Stereoisomeric aldoses are distinguished by trivial names, rather than by systematic designations Enantiomers have the same names but different D,L prefixes R,S designations are difficult to work with when there are multiple similar chirality centers Systematic methods for drawing and recalling structures are based on the use of Fischer projections Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 14 Four Carbon Aldoses Aldotetroses have two chirality centers There are 4 stereoisomeric aldotetroses, two pairs of enantiomers: erythrose and threose D-erythrose is a a diastereomer of D-threose and Lthreose Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 15 Minimal Fischer Projections In order to work with structures of aldoses more easily, only essential elements are shown OH at a chirality center is “” and the carbonyl is an arrow The terminal OH in the CH2OH group is not shown Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 16 Aldopentoses Three chirality centers and 23 = 8 stereoisomers, four pairs of enantiomers: ribose, arabinose, xylose, and lyxose Only D enantiomers will be shown Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 17 Systematic Drawing A chirality center is added with each CHOH adding twice the number of diastereomers and enantiomers Each diastereomer has a distinct name Start with the fact that they are D Go up to next center in 2 sets of 2 Finish with alternating pairs Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 18 Apply to Aldhexoses There are eight sets of enantiomers (from four chirality centers) Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 19 25.4 Configurations of the Aldohexoses 8 pairs of enantiomers: allose, altrose, glucose, mannose, gulose, idose, galactose, talose Name the 8 isomers using the mnemonic "All altruists gladly make gum in gallon tanks" Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 20 25.5 Cyclic Structures of Monosaccharides: Hemiacetal Formation Alcohols add reversibly to aldehydes and ketones, forming hemiacetals Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 21 Internal Hemiacetals of Sugars Intramolecular nucleophilic addition creates cyclic hemiacetals in sugars Five- and six-membered cyclic hemiacetals are particularly stable Five-membered rings are furanoses. Six-membered are pyanoses Formation of the the cyclic hemiacetal creates an additional chirality center giving two diasteromeric forms, desigmated and b These diastereomers are called anomers The designation indicates that the OH at the anomeric center is on the same side of the Fischer projection structure as hydroxyl that designates whether the structure us D or L Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 22 Fischer Projection Structures of Anomers: Allopyranose from Allose Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 23 Converting to Proper Structures The Fischer projection structures must be redrawn to consider real bond lengths Note that all bonds on the same side of the Fischer projection will be cis in the actual ring structure Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 24 Conformations of Pyranoses Pyranose rings have a chair-like geometry with axial and equatorial substituents Rings are usually drawn placing the hemiacetal oxygen atom at the right rear Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 25 25.6 Monosaccharide Anomers: Mutarotation The two anomers of D-glucopyranose can be crystallized and purified -D-glucopyranose melts at 146° and its specific rotation, []D = 112.2°; b-D-glucopyranose melts at 148–155°C a specific rotation of []D = 18.7° Rotation of solutions of either pure anomer slowly change due to slow conversion of the pure anomers into a 37:63 equilibrium mixture ot :b called mutarotation Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 26 Mechanism of Mutarotation Glucose Occurs by reversible ring-opening of each anomer to the open-chain aldehyde, followed by reclosure Catalyzed by both acid and base Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 27 25.7 Reactions of Monosaccharides OH groups can be converted into esters and ethers, which are often easier to work with than the free sugars and are soluble in organic solvents. Esterification by treating with an acid chloride or acid anhydride in the presence of a base All OH groups react Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 28 Ethers Treatment with an alkyl halide in the presence of base—the Williamson ether synthesis Use silver oxide as a catalyst with base-sensitive compounds Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 29 Glycoside Formation Treatment of a monosaccharide hemiacetal with an alcohol and an acid catalyst yields an acetal in which the anomeric OH has been replaced by an OR group b-D-glucopyranose with methanol and acid gives a mixture of and b methyl D-glucopyranosides Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 30 Glycosides Carbohydrate acetals are named by first citing the alkyl group and then replacing the -ose ending of the sugar with –oside Stable in water, requiring acid for hydrolysis Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 31 Selective Formation of C1-Acetal Synthesis requires distinguishing the numerous OH groups Treatment of glucose pentaacetate with HBr converts anomeric OH to Br Addition of alcohol (with Ag2O) gives a b glycoside (Koenigs–Knorr reaction) Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 32 Koenigs-Knorr Reaction Mechanism and b anomers of tetraacetyl-D-glucopyranosyl bromide give b -glycoside Suggests either bromide leaves and cation is stabilized by neighboring acetyl nucleophile from side Incoming alcohol displaces acetyl oxygen to give b glycoside Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 33 Reduction of Monosaccharides Treatment of an aldose or ketose with NaBH4 reduces it to a polyalcohol (alditol) Reaction via the open-chain form in the aldehyde/ketone hemiacetal equilibrium Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 34 Oxidation of Monosaccharides Aldoses are easily oxidized to carboxylic acids by: Tollens' reagent (Ag+, NH3), Fehling's reagent (Cu2+, sodium tartrate), Benedict`s reagent (Cu2+ sodium citrate) Oxidations generate metal mirrors; serve as tests for “reducing” sugars (produce metallic mirrors) Ketoses are reducing sugars if they can isomerize to aldoses Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 35 Oxidation of Monosaccharides with Bromine Br2 in water is an effective oxidizing reagent for converting aldoses to carboxylic acid, called aldonic acids (the metal reagents are for analysis only) Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 36 Formation of Dicarboxylic Acids Warm dilute HNO3 oxidizes aldoses to dicarboxylic acids, called aldaric acids The CHO group and the terminal CH2OH group are oxidized to COOH Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 37 Chain Lengthening: The Kiliani– Fischer Synthesis Lengthening aldose chain by one CH(OH), an aldopentose is converted into an aldohexose Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 38 Kiliani-Fischer Synthesis Method Aldoses form cyanohydrins with HCN Follow by hydrolysis, ester formation, reduction Modern improvement: reduce nitrile over a palladium catalyst, yielding an imine intermediate that is hydrolyzed to an aldehyde Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 39 Stereoisomers from Kiliani-Fischer Synthesis Cyanohydrin is formed as a mixture of stereoisomers at the new chirality center, resulting in two aldoses Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 40 Chain Shortening: The Wohl Degradation Shortens aldose chain by one CH2OH Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 41 25.8 Stereochemistry of Glucose: The Fischer Proof (1891) Chemical analysis revealed that (+)-glucose has the formula C6H12O6, and is linear with OH on each carbon except carbonyl of aldehyde Such a structure has four chirality centers and can be any one of 16 possible stereoisomers Since D and L could not be set, there were 8 possibilities to distinguish Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 42 Possible Structures of D-Glucose Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 43 Fischer’s Proof – Elongation of Arabinose Arabinose, an aldopentose, is converted by Kiliani–Fischer chain extension into a mixture of glucose and mannose Glucose and mannose must differ only at C2 Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 44 Fischer’s Proof – Oxidation with HNO3 Arabinose is oxidized by warm HNO3 to an optically active aldaric acid Only B and D give optically active product Arabinose must be either B or D Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 45 Fischer’s Proof: Oxidation of Hexoses with HNO3 These could all come from arabinose Glucose and mannose oxidize to optically active dicarboxylic acids Only structures 3 and 4 are possible Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 46 Fischer’s Proof: Interchanging Ends Reveals the Answer Oxidation with nitric acid followed by reduction gives two products from glucose and only one from mannose This is equivalent to putting aldehyde at C-6 Structure 4 must be mannose since it would give itself and 3 must be glucose Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 47 25.9 Disaccharides A disaccharide combines a hydroxyl of one monosaccharide in an acetal linkage with another A glycosidic bond between C1 of the first sugar ( or b) and the OH at C4 of the second sugar is particularly common (a 1,4 link) Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 48 Maltose and Cellobiose Maltose: two D-glucopyranose units with a 1,4--glycoside bond (from starch hydrolysis) Cellobiose: two D-glucopyranose units with a 1,4-b-glycoside bond (from cellulose hydrolysis) Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 49 Hemiacetals in Disaccharides Maltose and cellobiose are both reducing sugars The and b anomers equilibrate, causing mutarotation Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 50 You Can’t Eat Cellobiose The 1-4’-b-D-glucopyranosyl linkage in cellobiose is not attacked by any digestive enzyme The 1-4’--D-glucopyrnaosyl linkage in maltose is a substrate for digestive enzymes and cleaves to give glucose Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 51 Lactose A disaccharide that occurs naturally in milk Lactose is a reducing sugar. It exhibits mutarotation It is 1,4’-b-D-galactopyranosyl-D-glucopyranoside The structure is cleaved in digestion to glucose and galactose Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 52 Sucrose “Table Sugar” is pure sucrose, a disaccharide that hydrolyzes to glucose and fructose Not a reducing sugar and does not undergo mutarotation (not a hemiacetal) Connected as acetal from both anomeric carbons (aldehyde to ketone) Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 53 25.10 Polysaccharides and Their Synthesis Complex carbohydrates in which very many simple sugars are linked Cellulose and starch are the two most widely occurring polysaccharides Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 54 Cellulose Consists of thousands of D-glucopyranosyl 1,4-b- glucopyranosides as in cellobiose Cellulose molecules form a large aggregate structures held together by hydrogen bonds Cellulose is the main component of wood and plant fiber Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 55 Starch and Glycogen Starch is a 1,4--glupyranosyl-glucopyranoside polymer It is digested into glucose There are two components amylose, insoluble in water – 20% of starch 1,4’--glycoside polymer amylopectin, soluble in water – 80% of starch Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 56 Amylopectin More complex in structure than amylose Has 1,6--glycoside branches approximately every 25 glucose units in addition to 1,4--links Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 57 Glycogen A polysaccharide that serves the same energy storage function in animals that starch serves in plants Highly branched and larger than amylopectin—up to 100,000 glucose units Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 58 Glycals Tetracetyl glucosyl bromide (see Glycosides) reacts with zinc and acetic acid to form a vinyl ether, a glycal (the one from glucose is glucal) Glycals undergo acid catalyzed addition reactions with other sugar hydroxyls, forming anhydro disaccharide derivatives Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 59 Synthesis of Polysaccharides – via Glycals Difficult to do efficiently, due to many OH groups Glycal assembly is one approach to being selective Protect C6 OH as silyl ether, C3OH and C4OH as cyclic carbonate Glycal C=C is converted to epoxide Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 60 Glycal Coupling React glycal epoxide with a second glycal having a free OH (with ZnCl2 catayst) yields a disaccharide The disaccharide is a glycal, so it can be epoxidized and coupled again to yield a trisaccharide, and then extended Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 61 25.11 Other Important Carbohydrates Deoxy sugars have an OH group is replaced by an H. Derivatives of 2-deoxyribose are the fundamental units of DNA (deoxyribonucleic acid) Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 62 Amino Sugars OH group is replaced by an NH2 Amino sugars are found in antibiotics such as streptomycin and gentamicin Occur in cartilage Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 63 25.12 Cell-Surface Carbohydrates and Carbohydrate Vaccines Polysaccharides are centrally involved in cell–cell recognition - how one type of cell distinguishes itself from another Small polysaccharide chains, covalently bound by glycosidic links to hydroxyl groups on proteins (glycoproteins), act as biochemical markers on cell surfaces, determining such things as blood type Based on McMurry, Organic Chemistry, Chapter 25, 6th edition, (c) 2003 64
