1 Chapter 25 Carbohydrates [Cn(H2O)n]Bioorganic Chemistry Spring 2006 Chapter 25 Carbohydrates [Cn(H2O)n] Importance of carbohydrates in nature DNA and RNA: genetic code;  1163 & 1164 top cellulose/chitin: structure & protection;  glycoconjugates: lipids; blood type;  classification by the number of sugars monosaccharides: glucose, fructose;  1086 top disaccharides: sucrose, lactose;  1111 top polysaccharides: cellulose, amylose;  BioorgChem-Chap25 Chapter 25

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5 monosaccharides BioorgChem-Chap25

6 disaccharides BioorgChem-Chap25

7 polysaccharides BioorgChem-Chap25

8 Classification of Carbohydrates (II)Bioorganic Chemistry Spring 2006 Classification of Carbohydrates (II) Classification by the number of carbons hexose: C6H12O6; glucose, fructose;  1089 pentose: C5H10O5; ribose, tetrose: C4H8O4; erythrose Classification by the C-1/2 functional group aldose vs ketose: aldehyde vs ketone;  1088 bottom glucose: aldohexose / fructose: ketohexose (carbohydrates) ribose (xylose): aldopentose / ribulose (xylulose): ketopentose pyranose vs furanose: 6- vs 5-ring;  1091 top glucopyranose vs glucofuranose BioorgChem-Chap25 Chapter 25

9 tetroses pentoses hexoses BioorgChem-Chap25

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12 Stereochemistry of CarbohydratesBioorganic Chemistry Spring 2006 Stereochemistry of Carbohydrates Stereochemistry: Fischer projection;  1087 top Section 7.8: vertical chain down & horizontal FGs up Haworth projection: from the edge;  1092 bottom correlation to D-(+)-glyceraldehyde:  1088 top small capitals for D/L: large capitals for R/S (italic) a penultimate carbon: amino acids, a-hydroxyacids irrespective of other configurations;  1089 irrespective of optical rotation: D-(+)-glucose vs D-(–)-ribose d vs l: dextrorotatory (+) vs levorotatory (–) BioorgChem-Chap25 Chapter 25

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16 Cyclization of MonosaccharidesBioorganic Chemistry Spring 2006 Cyclization of Monosaccharides Favorable hemiacetals:  1090 bottom intramolecular vs intermolecular: favorable DS 6- vs 5-ring: thermodynamic (DH) vs kinetic;  1091 top equilibrium depends on monosaccharides:  1089 Anomers: a- & b-OH at C-1;  1092 top equilibrium ratio: relative stability;  1093 bottom mutarotation: [a]D at equilibrium;  1094 Prob. 25.1 anomeric effect: unusual stability of an axial alkoxy group configuration assignment by Karplus correlation Jax-ax (8-10 Hz), Jax-eq (eq-eq) (2-3 Hz);  1096 bottom BioorgChem-Chap25 Chapter 25

17 conf:  747 Table 18.1 & 775 bottom BioorgChem-Chap25

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19 (diastereomers; epimers)(anomeric carbons) (diastereomers; epimers) BioorgChem-Chap25

20 (equatorial) (axial) (36.4%) [a]D +112.2 mp 146 oC (63.6%) [a]D +18.7BioorgChem-Chap25

21 ‘A’ value (axial strain energy): DGOH = – RT lnK ( 204)K = [eq]/[ax] = e(900/1.987x298) = 4.572; [eq]:[ax] ≈ 82:18 EWGs at C-1 (anomeric carbon): axial position favored origins of the anomeric effect: other examples reduced dipole-dipole repulsion & p-s* resonance BioorgChem-Chap25

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23 vicinal coupling BioorgChem-Chap25

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25 Reactions of MonosaccharidesBioorganic Chemistry Spring 2006 Reactions of Monosaccharides Oxidations & Reductions: aldehydes & alcohols oxidation: HNO3 at low temp, a,w-diacid;  1095 top oxidation: Br2 in H2O, only C-1 acid;  1097 top oxidation: reducing sugars (ketoses);  1097 bottom reduction: aldehydes to alcohols:  1098 top Nucleophilic OH: peracetylation;  1099 mid Enolization: acidic or basic;  1098 bottom Gylcoside formation: acidic;  1099 bottom natural glycosides: salicin, disaccharides BioorgChem-Chap25 Chapter 25

26 (not optically active)BioorgChem-Chap25

27 (citrate) (tartrate) BioorgChem-Chap25

28 (no D form) (sugarless gum) BioorgChem-Chap25

29 BioorgChem-Chap25

30 [mechanism] BioorgChem-Chap25

31 MeOH (b-glucoside) Conf: Figure 18.5, p 776 BioorgChem-Chap25

32 Structure Proof of MonosaccharidesBioorganic Chemistry Spring 2006 Structure Proof of Monosaccharides Configuration of (+)-glucose (aldohexose) Kiliani-Fischer synthesis: two isomeric one-C higher aldoses form lower aldoses;  1095 top K-F synthesis of D-glucose and D-mannose from D-arabinose: 4 possible sets;  1107 oxidation of D-glucose and D-mannose with HNO3: optically active aldaric acids;  1106 bot & 1108 top HNO3 oxidation of D-arabinose: active;  1108 bot HNO3 oxidation of L-gulose & D-glucose → 13 vs only one aldohexose 8 (16)→ 15;  1109 All altruists gladly make gum in a gallon tank:  1089 BioorgChem-Chap25 Chapter 25

33 cyanohydrin BioorgChem-Chap25

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35 (not optically active)BioorgChem-Chap25

36 (not optically active)BioorgChem-Chap25

37 / H BioorgChem-Chap25

38 Other Reactions of MonosaccharidesBioorganic Chemistry Spring 2006 Other Reactions of Monosaccharides Ruff-Fenton degradation: OH-CH-CHO → CHO one-C less aldose: H-O-O-H, Fe3+; radical (•OH) Osazone formation with 3 eq. of PhNHNH2 the same bis(phenylhydrzone) from 2-epi-aldose Conversion of an aldose into its 2-epimer epimerization of aldonic acids with pyridine Correlation of absolute configuration: chemical D-(-)-glyceraldehyde with D-(-)-tartaric acid X-ray structure of Na/Rb L-(+)-tartrate: Bijvoet (1951) BioorgChem-Chap25 Chapter 25

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40 D-(-)-ribose D-(-)-arabinose BioorgChem-Chap25

41 D-(+)-glucose D-(+)-mannose BioorgChem-Chap25

42 meso-tartaric acid D-(-)-tartaric acid BioorgChem-Chap25

43 Disaccharides (I) (+)-maltose: hydrolysis of starch, C12H22O11Bioorganic Chemistry Spring 2006 Disaccharides (I) (+)-maltose: hydrolysis of starch, C12H22O11 reducing sugar, mutarotation, osazone: hemiacetal 2 glucose & a-glycosidic bond: hydrolysis & maltase (+)-cellobiose: from cellulose, C12H22O11 2 glucose & b-glycosidic bond: hydrolysis & emulsin BioorgChem-Chap25 Chapter 25

44 4-O-(a-D-glucopyranosyl)-D-glucopyranose 4-O-(b-D-glucopyranosyl)-D-glucopyranose BioorgChem-Chap25

45 Disaccharides (II) (+)-lactose: in milk & by-product of cheeseBioorganic Chemistry Spring 2006 Disaccharides (II) (+)-lactose: in milk & by-product of cheese into lactic acid by Lactobacillus bulgaricus galactose-glucose by a b-glycosidic bond: emulsin (+)-sucrose: sugar cane, non-reducing sugar a-glucopyranoside & b-fructofuranoside: acetal synthesis of sucrose by R. U. Lemieux in 1953: the Mount Everest of organic chemistry hydrolysis & invertase: (+) → (-); inversion of sucrose (+)-sucrose → inverta sugar [(+)-glucose +52.7, ‘dextrose’ & (-)-fructose -92.4, ‘levulose’] BioorgChem-Chap25 Chapter 25

46 4-O-(b-D-galactopyranosyl)-D-glucopyranose a-D-glucopyranosyl b-D-fructofuranoside b-D-fructofuranosyl a-D-glucopyranoside BioorgChem-Chap25

47 Polysaccharides Cellulose: (C6H10O5)n; wood and plant fibersBioorganic Chemistry Spring 2006 Polysaccharides Cellulose: (C6H10O5)n; wood and plant fibers hydrolysis of permethylated cellulose: 2,3,6-tri-O-methyl-D-glucose; 4-O-b-glucoside; non-reducing MW 250,000 – 1,000,000: > 1500 glucose units insoluble & tasteless, > 1015 kg from CO2 & H2O: biomass Starch: (C6H10O5)n; food reserve of plants 20% amylose (soluble), 80% amylopectin (insoluble) hydrolysis to dextrin → (+)-maltose → (+)-glucose > 1000 (amylose) to 106 glucose units (amylopectin)-every branch/20-30 glucose glycogen: food reserve in animals;  1113 top similar to amylopectin but every branch/8-10 glucose units BioorgChem-Chap25 Chapter 25

48 cellulose [4-O-(b-D-glucoopyranosyl)]BioorgChem-Chap25

49 BioorgChem-Chap25

50 Other Carbohydrates Cyclodextrins: oligosaccharides of > 6 glucoseBioorganic Chemistry Spring 2006 Other Carbohydrates Cyclodextrins: oligosaccharides of > 6 glucose by amylase of Bacillus macerans: a-(6), b-(7), g-(8) cyclic pail-shaped 1,4-a-linkage (4.5 Å across): host-guest complex; polar outside/non-polar inside enzyme models: binding and then reaction of substrates Amino sugars: -NHR;  1114 top & chitin Deoxy sugras: -H;  1114 bottom Glycoproteins: sugar-protein;  1115 top glycolipids: sugar-lipid;  1113 top Sweeteners: with adjacent OHs (glycol) artificial sweeteners:  1104 top BioorgChem-Chap25 Chapter 25

51 a-cyclodextrin (6 glucose units)top view side view a-cyclodextrin (6 glucose units) [18-crown-6: 2.7 Å (K+: 2.66 Å)] BioorgChem-Chap25

52 (chitin) O-2-deoxy-2-(methylamino)-a-L-glucopyranosyl-(1→2)-O-5-deoxy-3-C-formyl-a-L-lyxofuranosyl- (1→4)-N,N’-bis(aminoiminomethyl)-D-streptamine BioorgChem-Chap25

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