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Carbohydrates: History, Definitions, and Concepts 1 Objectives: • To understand history of carbohydrate & its nomenclature • To be familiar with selected definitions and concepts • To be able to manipulate stereochemistry models of hexose rings Chronological Summary of Carbohydrate Uses & Knowledge 2 10,000 BCE 6000 BCE 6000 BCE 4000 BCE 1500 BCE 1000 BCE 100 CE 700 CE 1600 CE 1700 CE 1792 CE 1802 CE Primitive sugarcane processing in New Guinea Sugarcane culture developed in India Cellulose, as cotton, is used by many cultures Starch is used as an adhesive for papyrus in Egypt Cotton cloth from India spreads to Persia and China Use of sucrose in candies, confections, and medicines in Egypt Paper is made for writing in China Paper is coated with starch paste to retain ink and provide strength Many sugar refineries developed in Europe Sugar beet is developed in Europe for obtaining sucrose A sugar is isolated from honey that is different from sucrose A sugar is found in grapes that is also different from sucrose 1808 CE Malus developed plane polarized light and observes optical rotation by carbohydrates Acid-hydrolyzed starch produces a sweet crystalline sugar Acid-hydrolyzed cellulose also produces a sweet crystalline sugar 1811 CE 1820 CE 1821 CE Production of dextrins by heating starch is discovered and leads to British Gums Adapted from John Robyt, Essentials of Carbohydrate Chemistry 3 Chronological Summary of Carbohydrate Uses & Knowledge 1838 CE The sugar from honey, grapes, starch, and cellulose is found to be identical and called glucose 1866 CE Kekule changes the name of glucose to dextrose because it rotates plane polarized light to the right 1870 CE Bayer and Fittig propose that the formula for glucose is HO-CH2-CH(OH)CH(OH)-CH(OH)-CH(OH)-CHO 1874 CE Le Bel and van’t Hoff independently develop the theory of optical rotation by asymmetric tetrahedral carbon atoms with four different groups around each carbon 1881 CE A sugar is crystallized from honey that is different from sucrose and glucose, It is named levulose because it rotates plane polarized light to the left 1886 CE Fructose, galactose, sorbose, and mannose are shown to have the same empirical formula C6H12 O6 1888 CE Glucose is shown to be a six-carbon polyhydroxy aldehyde 1888 CE Fischer embarks on the determination of the structure of carbohydrates 1891 CE Fischer reports the structure of glucose, mannose, fructose, and arabinose 1892-1900 CE Controversies and discussions about intramolecular hemiacetals forming two isomeric acetals (glycosides) 1920-1930 CE The carbohydrate group led by Haworth demonstrated the size of carbohydrate rings to be primarily six-membered pyranoses and propose a six-membered hexagon to represent the carbohydrates Adapted from John Robyt, Essentials of Carbohydrate Chemistry 1 4 Development of Carbohydrate Nomenclature – Earlier Approach In the early nineteenth century, individual sugars were often named after their source, e.g. grape sugar for glucose, cane sugar for saccharose (sucrose) “Glucose” was coined in 1838; Kekulé in 1866 proposed the name “dextrose” because glucose is dextrorotatory*, and the levorotatory* “fruit sugar” (fructose) was for some time named “levulose” Very early, consensus was reached that sugars should be named with the ending “-ose”, and by combination with the French word “cellule” for cell the term cellulose was coined, long before the structure was known The term “carbohydrate” (French “hydrate de carbone”) was applied originally to monosaccharides, in recognition of the fact that their empirical composition can be expressed as Cn(H2O)n. However the term is now used generically in a wider sense * Dextrorotatory (Levorotatory): Of or relating to an optically active chemical that rotates the plane of polarized light to the right (left) , or clockwise (counterclockwise) Adapted from IUPAC Nomenclature of Carbohydrates (1996) http://www.chem.qmul.ac.uk/iupac/2carb/ 5 Development of Carbohydrate Nomenclature – Emil Fischer Emil Fischer began carbohydrate studies in 1880, assigned the relative configurations of most known sugars and had also synthesized many sugars. He and others laid the foundations of a terminology still in use, based on the terms triose, tetrose, pentose, and hexose. The concept of stereochemistry, developed since 1874 by van't Hoff and Le Bel, had a great impact on carbohydrate chemistry. Emil Fischer introduced the classical projection formula for sugars, with a standard orientation (Fischer projection: carbon chain vertical, carbonyl group at the top). He assigned to the dextrorotatory glucose the projection with the OH group at C-5 pointing to the right, well knowing that there was a 50% chance that this was wrong. Much later (Bijvoet, 1951), it was proved CORRECT!!. Rosanoff in 1906 selected the enantiomeric glyceraldehydes as the point of reference. Any sugar derivable by chain lengthening from what is now known as D-glyceraldehyde belongs to the D series, a convention still in use. Adapted from IUPAC Nomenclature of Carbohydrates (1996) http://www.chem.qmul.ac.uk/iupac/2carb/ Emil Fischer (1852-1919) 6 Fischer began his career as student of Adoph v. Baeyer *, in 1879 he became professor in München (1879), Erlangen (1881), Würzburg (1885), and Berlin (1892). In 1883 Fischer found a synthesis for indol, later he did research on purines (1880-84), on sugars, on barbituric acid, and on aminoacids. In 1902 he was awarded the Nobel Prize for chemistry, in recognition of the extraordinary services he has rendered by his work on sugar and purine syntheses . Affiliation: Berlin University * Adoph v. Baeyer was awarded Nobel Prize for Chemistry in 1905 2 7 Development of Carbohydrate Nomenclature – Commissions In 1939 American Chemical Society formed a committee and laid the foundations of modern systematic nomenclature for carbohydrates and derivatives: numbering of the sugar chain, the use of D and L and α and β, and the designation of stereochemistry by italicized prefixes. In 1952, a joint British-American committee published “Rules for Carbohydrate Nomenclature”. Its revised version was endorsed in 1963 by the American Chemical Society and by the Chemical Society in Britain. This report led the IUPAC Commission on Nomenclature of Organic Chemistry to consider the preparation of a set of IUPAC Rules for Carbohydrate Nomenclature. This was done jointly with the IUPAC-IUB Commission on Biochemical Nomenclature, and resulted in the “Tentative Rules for Carbohydrate Nomenclature, Part I, 1969”, published in 1971/72. Currently used is a revision of the 1971 document Adapted from IUPAC Nomenclature of Carbohydrates (1996) http://www.chem.qmul.ac.uk/iupac/2carb/ 8 Development of Carbohydrate Nomenclature – Commissions For more details about IUPAC carbohydrate nomenclature, please go to: http://www.chem.qmul.ac.uk/iupac/2carb/ Carbohydrate Definitions and Concepts: the List 9 Carbohydrates Aldoses and ketoses Configurational atom Monosaccharides Chiral carbon atom Isomerization Cyclic form Anomeric forms Conformation of cyclic forms Haworth representation Ring equilibrium Deoxy sugars Alditols Uronic acids Amino sugars Aldonic acids Aldaric acids Glycosides Polysaccharides Oligosaccharides 3 Carbohydrate Definitions and Concepts 10 Carbohydrates The generic term “carbohydrate” includes monosaccharides, oligosaccharides and polysaccharides as well as substances derived from monosaccharides by: • Reduction of the carbonyl group (alditols) • Oxidation of one or more terminal groups to carboxylic acids • Replacement of one or more hydroxy group(s) by a hydrogen atom, an amino group, or a thiol group “Carbohydrate” also includes derivatives of these compounds The term “sugar” is frequently applied to monosaccharides and lower oligosaccharides Adapted from IUPAC Nomenclature of Carbohydrates (1996) http://www.chem.qmul.ac.uk/iupac/2carb/ Carbohydrate Definitions and Concepts 11 Monosaccharides Parent monosaccharides are • Polyhydroxy aldehydes H-[CHOH]n-CHO, or • Polyhydroxy ketones H-[CHOH]n-CO-[CHOH]m-H • With three or more carbon atoms The generic term “monosaccharide” (as opposed to oligosaccharide or polysaccharide) denotes a single unit, without glycosidic connection to other such units “Monosaccharide” includes aldoses, dialdoses, aldoketoses, ketoses and diketoses, as well as deoxy sugars and amino sugars, and their derivatives, provided that the parent compound has a carbonyl group. Adapted from IUPAC Nomenclature of Carbohydrates (1996) http://www.chem.qmul.ac.uk/iupac/2carb/ Carbohydrate Definitions and Concepts 12 Aldoses and ketoses Monosaccharides with an aldehydic carbonyl or potential aldehydic carbonyl group* are called aldoses Monosaccharides with a ketonic carbonyl or potential ketonic carbonyl group* are called ketoses * “Potential aldehydic (ketonic) carbonyl group” refers to the hemiacetal (hemiketal) group arising from ring closure Adapted from IUPAC Nomenclature of Carbohydrates (1996) http://www.chem.qmul.ac.uk/iupac/2carb/ 4 Carbohydrate Definitions and Concepts 13 Chiral carbon atom One of the distinguishing features of carbohydrates is that they contain one or more chiral carbon atoms A chiral carbon atom has four different groups attached to it A structure containing a chiral carbon atom and its mirror image are non-superimposable CHO HO CHO H H OH HO L-glyceraldehyde Mirror OH D-glyceraldehyde Carbohydrate Definitions and Concepts 14 Configurational atom A monosaccharide is assigned to the D or the L series according to the configuration at the highest-numbered centre of chirality. This asymmetrically substituted carbon atom is called the “configurational atom”. If the hydroxy group projects to the right in the Fischer projection, the sugar belongs to the D series and receives the prefix D-. If the hydroxy group projects to the left, the sugar belongs to the L series and receives the prefix L-. 1 2 3 4 5 6 D-Glucose L-Glucose Adapted from IUPAC Nomenclature of Carbohydrates (1996) http://www.chem.qmul.ac.uk/iupac/2carb/ Carbohydrate Definitions and Concepts 15 Aldoses Trivial names (with three-letter abbreviations in parentheses) and structures (in the aldehydic, acyclic form) of the aldoses with three to six carbon atoms. Only the D-forms are shown; the L-forms are the mirror images Adapted from IUPAC Nomenclature of Carbohydrates (1996) http://www.chem.qmul.ac.uk/iupac/2carb/ 5 Carbohydrate Definitions and Concepts 16 Ketoses Structures, with systematic and trivial names, of the 2-ketoses with three to six carbon atoms Adapted from IUPAC Nomenclature of Carbohydrates (1996) http://www.chem.qmul.ac.uk/iupac/2carb/ Carbohydrate Definitions and Concepts 17 Isomerization CHO HO OH HO H H OH OH D-glucose CHO OH O OH HO H HO HO HO HO OH OH OH OH OH OH OH OH OH OH OH OH OH OH trans-enediol OH D-fructose cis-enediol D-mannose Industry uses glucose isomerase to convert glucose (dextrose) to fructose to produce high fructose corn syrup (HFCS). When fructose is hydrogenated, it produces both sorbitol ($0.2/lb) and mannitol ($2.0/lb) 18 Carbohydrate Definitions and Concepts Monosaccharides Browser http://www.beechtreecommon.org/biochemistry/monosaccharide/ 6 Carbohydrate Definitions and Concepts 19 Cyclic forms The Fischer projection of cyclic form α-D-Glucooxirose α-D-Glucopyranose α-D-Glucooxetose Modified Fischer projection of α-D-Glucopyranose α-D-Glucofuranose α-D-Glucoseptanose Adapted from IUPAC Nomenclature of Carbohydrates (1996) http://www.chem.qmul.ac.uk/iupac/2carb/ Carbohydrate Definitions and Concepts 20 Haworth representation A perspective drawing of a simplified model. The ring is orientated almost perpendicular to the plane of the paper, but viewed from slightly above so that the edge closer to the viewer is drawn below the more distant edge, with the oxygen behind and C-1 at the right-hand end. To define the perspective, the ring bonds closer to the viewer are often thickened The new centre of chirality generated by hemiacetal ring closure is called the anomeric centre Adapted from IUPAC Nomenclature of Carbohydrates (1996) http://www.chem.qmul.ac.uk/iupac/2carb/ Carbohydrate Definitions and Concepts 21 Anomeric forms; use of α and β 1. The anomeric centre: the new centre of chirality generated by hemiacetal ring closure 2. The two stereoisomers are referred to as anomers, designated α or β according to the configurational relationship between the anomeric centre and the anomeric reference atom 3. In the α anomer, the exocyclic oxygen atom at the anomeric centre is formally cis, in the Fischer projection, to the oxygen attached to the anomeric reference atom; in the β anomer these oxygen atoms are formally trans trans cis Anomeric reference atom Anomeric reference atom α-D-Glucopyranose β-D-Glucopyranose Adapted from IUPAC Nomenclature of Carbohydrates (1996) http://www.chem.qmul.ac.uk/iupac/2carb/ 7 Carbohydrate Definitions and Concepts 22 Mixtures of anomers In solution, most simple sugars and many of their derivatives occur as equilibrium mixtures The presence of a mixture of two anomers of the same ring size may be indicated by the notation α,β-, e.g. α,β-D-glucose In formula, mixture of anomers is expressed by separating the representation of the ligands at the anomeric centre from the α and β bonds [see (a) and (c)], or by use of a wavy line [see (b) and (d)] (particularly if hydrogen atoms are omitted). α,β-D-glucopyranose α,β-D-fructofuranose 6-phosphate Adapted from IUPAC Nomenclature of Carbohydrates (1996) http://www.chem.qmul.ac.uk/iupac/2carb/ Carbohydrate Definitions and Concepts 23 Ring equilibrium β-D-glucopyranose, 62% α-D-glucopyranose, 37% Open chain α-D-glucofuranose, 0.5% β-D-glucofuranose, 0.5% Carbohydrate Definitions and Concepts 24 Conformation of cyclic forms The conformation, i.e. the (approximate) spatial arrangement of the ring atoms of a monosaccharide in the cyclic form, may be indicated by an italic capital letter designating the type of ring shape, and numerals, distinguishing the variants. The conformational descriptor is joined to the end of the name of the monosaccharide by a hyphen. Conformation of six-member rings Chairs Boats Skews Half-chairs α-D-Glucopyranose-4C1 Let’s look at the stereochemistry models! Adapted from IUPAC Nomenclature of Carbohydrates (1996) http://www.chem.qmul.ac.uk/iupac/2carb/ 8 Carbohydrate Definitions and Concepts 25 Deoxy sugars Monosaccharides in which an alcoholic hydroxy group has been replaced by a hydrogen atom are called deoxy sugars Several deoxy sugars have trivial names established by long usage, e.g. fucose (Fuc), quinovose (Qui) and rhamnose (Rha). They are illustrated below in the pyranose form α-L-Fucopyranose or 6-Deoxy-α-L-galactopyranose β-D-Quinovopyranose or 6-Deoxy-β-D-glucopyranose L-Rhamnopyranose or 6-Deoxy-L-mannopyranose Adapted from IUPAC Nomenclature of Carbohydrates (1996) http://www.chem.qmul.ac.uk/iupac/2carb/ Carbohydrate Definitions and Concepts 26 Ribose & Deoxyribose Ribose is a pentose that is critical to living creatures. It is a component of the RNA (Ribonucleic acid) that is used for genetic transcription, and is related to deoxyribose. It is also a component of ATP, NADH, and several other chemicals that are critical to the metabolic process Deoxyribose (more precisely 2-deoxyribose) is a pentose derived from ribose by the replacement of the hydroxyl group at the 2 position with hydrogen, leading to the net loss of an oxygen. It is a component of DNA (Deoxyribonucleic acid) Ribose Deoxyribose Carbohydrate Definitions and Concepts 27 Amino sugars Monosaccharides in which an alcoholic hydroxy group has been replaced by an amino group are called amino sugars. When the hemiacetal hydroxy group is replaced, the compounds are called glycosylamines 2-Amino-2-deoxy-D-glucopyranose (D-glucosamine) Adapted from IUPAC Nomenclature of Carbohydrates (1996) http://www.chem.qmul.ac.uk/iupac/2carb/ 9 Carbohydrate Definitions and Concepts 28 Alditols The polyhydric alcohols arising formally from the replacement of a carbonyl group in a monosaccharide with a CHOH group are termed alditols. Alditols are named by changing the suffix “-ose” in the name of the corresponding aldose into “-itol” D-Glucitol (Sorbitol) Adapted from IUPAC Nomenclature of Carbohydrates (1996) http://www.chem.qmul.ac.uk/iupac/2carb/ Carbohydrate Definitions and Concepts 29 Aldonic acids Monocarboxylic acids formally derived from aldoses by replacement of the aldehydic group by a carboxy group are termed aldonic acids Aldonic acids are divided into aldotrionic acid, aldotetronic acids, aldopentonic acids, aldohexonic acids, etc., according to the number of carbon atoms in the chain. The names of individual compounds of this type are formed by replacing the ending “-ose” of the systematic or trivial name of the aldose by “-onic acid” D-Gluconic acid D-Gluconate Adapted from IUPAC Nomenclature of Carbohydrates (1996) http://www.chem.qmul.ac.uk/iupac/2carb/ Carbohydrate Definitions and Concepts 30 Uronic acids Monocarboxylic acids formally derived from aldoses by replacement of the CH2OH group with a carboxy group are termed uronic acids The names of these compounds are formed by replacing (a) the “-ose” of the name of the aldose by “-uronic acid” (b) the “-oside” of the name of the glycoside by “-osiduronic acid” (c) the “-osyl” of the name of the glycosyl group by “-osyluronic acid” D-Glucuronic acid Adapted from IUPAC Nomenclature of Carbohydrates (1996) http://www.chem.qmul.ac.uk/iupac/2carb/ 10 Carbohydrate Definitions and Concepts 31 Aldaric acids The dicarboxylic acids formed from aldoses by replacement of both terminal groups (CHO and CH2OH) by carboxy groups are called aldaric acids Names of individual aldaric acids are formed by replacing the ending “-ose” of the name of the parent aldose by “-aric acid” L-Altraric acid D-Glucaric acid Adapted from IUPAC Nomenclature of Carbohydrates (1996) http://www.chem.qmul.ac.uk/iupac/2carb/ Carbohydrate Definitions and Concepts 32 Glycosides Glycosides are acetals arising by elimination of water between the hemiacetal or hemiketal hydroxy group of the cyclic form of sugar and a hydroxy group of a second compound. The bond between the two components is called a glycosidic bond (linkage) The term “glycoside” may be used to cover compounds in which the anomeric hydroxy group is replaced not only by a group -OR, but also a group -SR (thioglycosides) The compound ROH from which the carbohydrate residue has been removed is often termed the aglycone, and the carbohydrate residue itself is sometimes referred to as the “glycone” Usually, glycosides can be named by replacing the terminal “-e” of the name of the corresponding cyclic form of the monosaccharide by “-ide” and preceding this, as a separate word, the name of the group R Methyl α-D-glucopyranoside Adapted from IUPAC Nomenclature of Carbohydrates (1996) http://www.chem.qmul.ac.uk/iupac/2carb/ Carbohydrate Definitions and Concepts 33 Oligosaccharides Oligosaccharides are compounds in which monosaccharide units are joined by glycosidic linkages According to the number of units, they are called disaccharides (DP2), trisaccharides (DP3), tetrasaccharides (DP4), pentasaccharides (DP5) etc. DP means “degree of polymerization” The term “oligosaccharide” is commonly used to refer to a defined structure as opposed to a polymer of unspecified length or a homologous mixture α-D-Glucopyranosyl-(1→6)-α-D-glucopyranosyl-(1→4)-D-glucopyranose (panose) Adapted from IUPAC Nomenclature of Carbohydrates (1996) http://www.chem.qmul.ac.uk/iupac/2carb/ 11 Carbohydrate Definitions and Concepts 34 Polysaccharides “Polysaccharide” is the name given to a macromolecule consisting of a large number of monosaccharide residues joined to each other by glycosidic linkages. Polysaccharides composed of only one kind of monosaccharide are described as homopolysaccharides. Similarly, if two or more different kinds of monomeric unit are present, the class name heteropolysaccharide may be used. A general term for a homopolysaccharide is obtained by replacing the ending “ose” of the sugar name by “-an”. For example: xylan for polymers of xylose, mannan for polymers of mannose, and galactan for polymers of galactose. Cellulose and starch are both glucans, as they are composed of glucose residues [3)-β-D-Glcp-(1→4)-βL-GlcpA-(1→4)-β-D-Glcp-(1→4)-α-L-Rhap-(1 →]n Gellan (a bacterial polysaccharide) Adapted from IUPAC Nomenclature of Carbohydrates (1996) http://www.chem.qmul.ac.uk/iupac/2carb/ 12