Copyright © 2014 by John Wiley & Sons, Inc. All rights reserved. Chapter 22 Carbohydrates Created By Prof. Gary F. Porter, Ph.D. Copyright © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. Table of Contents Introduction Monosaccharides Mutarotation Glycosidic Formation Other Reactions of Monosaccharides Oxidation Reactions of Monosaccharides Reduction of Monosaccharides: Alditols Reactions of Monosaccharides with Phenylhydrazine: Osazone Synthesis of Monosaccharides 10. Degradation of Monosaccharides 11. The D Family of Aldoses 12. Disaccharides 13. Polysaccharides 14. Other Biologically Important Sugars 15. Sugars that Contain Nitrogen © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 1. Introduction 1a. Classification of Carbohydrates Carbohydrates Are polyhydroxyl aldehydes and ketones in the monomeric form and Exist in hemiacetal and acetal forms. Sugars are Monosaccharides - 1 monomeric unit Disaccharides - 2 monomeric units) Oligosaccharides - 3 to 10 monomeric units Polysaccharides - more than 10 monomeric units © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 2. Monosaccharides 2A. Classification of Monosaccharides Aldose - contains an aldehyde group Ketose - contains a ketone group Triose - contains 3 carbons Tetrose - contains 4 carbons Aldopentose - contains an aldehyde & 5 carbons Ketohexose - contains a ketone & 6 carbons © 2014 by John Wiley & Sons, Inc. All rights reserved.

2A. Classification of Monosaccharides Practice Problem 22.1 How many chirality centers are contained in (a) the aldotetrose and (b) the ketopentose above? (c) How many stereoisomers would you expect from each general structure? © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 2. Monosaccharides 2B. D- and L- Designations of Monosaccharides Identify the molecule which has a chirality center. © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 2. Monosaccharides 2B. D- and L- Designations of Monosaccharides Two enantiomeric forms of glyceraldehyde exist. We designate D- and L- for these trioses. D-Form L-Form Note: These designations give no indication of their dexo- vs. levorotatory nature. © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 2. Monosaccharides 2B. D- and L- Designations of Monosaccharides Note which carbon determines the D- & L- designations © 2014 by John Wiley & Sons, Inc. All rights reserved.

2B. D- and L- Designations of Monosaccharides Practice Problem 22.2 Identify a three-dimensional formula for the above and designate each as a D- or L- sugar. © 2014 by John Wiley & Sons, Inc. All rights reserved.

2C. Structural Formulas for Monosaccharides Fischer projections are useful for monosaccharide analysis. Note the two orientations of the blue oxygens below. Haworth formulas are useful because monosaccharides exist in the cyclic form. © 2014 by John Wiley & Sons, Inc. All rights reserved.

2C. Structural Formulas for Monosaccharides Formulas 6 and 7 illustrate the three-dimensional configurations of the molecules. © 2014 by John Wiley & Sons, Inc. All rights reserved.

2C. Structural Formulas for Monosaccharides These diastereomers Differ only at the hemiacetal carbon, and Are the α and β anomers of D-glucose. Ketoses form cyclic acetals with the same two anomeric forms. © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 3. Mutarotation The α and β anomers are in equilibrium. The value of that equilibrium is the mutarotation value. © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 3. Mutarotation This equilibrium favors the more stable β anomer. This shift in equilibrium is called the anomeric effect. Note: The open-chair form is negligible at equilibrium. This equilibrium favors the more stable α anomer. © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 4. Glycosidic Formation Formation of glycosidic bonds are Acid-catalyzed and Include the addition of methanol. Note: The acid catalyzed addition of methanol on salicin produces aspirin. © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 4. Glycosidic Formation Hydrolysis of a glycosidic bond Does not react in base, and Is acid-catalyzed. © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 5. Other Reactions of Monosaccharides 5A. Enolization, Tautomerization, and Isomerization Base facilitates isomerization of monosaccharides. Enolization creates epimers. D-Glucose to D-Mannose Tautomerization creates structural isomers. D-Glucose to D-Fructose Note: Formation of a glysoside prevents enolization. © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 5. Other Reactions of Monosaccharides 5A. Enolization, Tautomerization, and Isomerization Tautomerization creates structural isomers D-Glucose to D- Fructose Note: Formation of a glycoside prevents enolization © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 5. Other Reactions of Monosaccharides 5C. Formation of Ethers © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 5. Other Reactions of Monosaccharides 5C. Formation of Ethers Exhaustive Methylation SN2 Mechanism Base-catalyzed © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 5. Other Reactions of Monosaccharides 5D. Conversions to Esters Base-catalyzed with pyridine or sodium acetate Treat with excess acetic anhydride © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 5. Other Reactions of Monosaccharides 5E. Conversion to Cyclic Acetals Are acid-catalyzed (H2SO4), Needs vicinal (adjacent) hydroxyls, Produces acetonides from acetone. © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 6. Oxidation Reactions of Monosaccharides Benedict’s Reagent: Reducing Sugars Aldoses & Ketose are reducing sugars. Anomeric methylated Aldoses & Ketoses are non-reducing sugars. © 2014 by John Wiley & Sons, Inc. All rights reserved.

22.6 Oxidation Reactions of Monosaccharides Benedict’s Reagent: Reducing Sugars Gives a positive test for Aldoses & Ketoses, and Gives a negative test for Non-reducing sugars. 22.6 Oxidation Reactions of Monosaccharides © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 6. Oxidation Reactions of Monosaccharides Tollens’ Reagent: Reducing Sugars (Aldoses vs. Ketoses) Gives a positive test for Aldoses, and Gives a negative test for Ketoses. Aldehyde + Ag+(NH3)2HO- Carboxylate + Ag(↓) Clear Soln. Mirrored Silver Surface © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 6. Oxidation Reactions of Monosaccharides Practice Problem 22.6 How might you distinguish between α-D-glucopyranose (i.e., D-glucose), methyl α-D-glucopyranoside, and α-D-fructofuranose. Sugars Benedict's Test Tollens’ Test α-D-glucopyranose Pos. or Neg. Me α-D-glucopyranoside α-D-fructofuranose © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 6. Oxidation Reactions of Monosaccharides 6B. Bromine Water: The Synthesis of Aldonic Acid Selectively oxidizes Aldehydes, Gives a positive Test for Aldose, and Gives a negative test for Ketose. © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 6. Oxidation Reactions of Monosaccharides 6C. Nitric Acid Oxidation: Aldaric Acids Oxidizes both –CHO and –CH2OH groups, Forms –COOH groups. © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 6. Oxidation Reactions of Monosaccharides 6D. Periodate Oxidations: Oxidative Cleavage of Polyhydroxyl Compounds Mechanism Stoichiometric cleavage © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 6. Oxidation Reactions of Monosaccharides 6D. Periodate Oxidations: Oxidative Cleavage of Polyhydroxyl Compounds © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 6. Oxidation Reactions of Monosaccharides Practice Problem 22.9 What products would you expect to be formed when each of the following compounds is treated with an appropriate amount of periodic acid? How many molar equivalents of HIO4 would be consumed in each case? Practice Problem 22.10 Show how periodic acid could be used to distinguish between an aldohexose and a ketohexose. What products would you obtain from each, and how many molar equivalents of HIO4 would be consumed? © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 7. Reduction of Monosaccharides: Alditols Reduction with NaBH4 Practice Problem 22.11 (a) Would you expect D-glucitol to be optically active? (b) Write Fischer projection formulas for all of the D-aldohexoses that would yield optically inactive alditols. © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 8. Reactions of Monosaccharides with Phenylhydrazine: Osazone Osazone The product is called a phenylasozone. Substitutions occur on C-1 and C-2. © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 8. Reactions of Monosaccharides with Phenylhydrazine: Osazone Epimers Differ in chirality at a single carbon. i.e., D-Glucose & D-Mannose Osazone Formation Results in loss of chirality at C2. © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 9. Synthesis of Monosaccharides Kiliani-Fischer Synthesis: Carbons in sugar chain are lengthened. Epimers are produced. Practice Problem 22.13 Cyanohydrin Hydrolysis Lactone forms (a) What are the structures of L-(+)-threose and L-(+)-erythrose? (b) What aldotriose would you use to prepare them in a Kiliani–Fischer synthesis? Reduction © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 10. Degradation of Monosaccharides The Ruff Degradation: Reduces the carbon chain by one carbon, and Is an oxidative decarboxylation. © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 11. The D Family of Aldoses Most naturally occurring aldoses belong to the D-family © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 12. Disaccharides 12A. Sucrose Is ordinary table sugar. Is found in photosynthetic plants. Glucose (as an α-pyranose) © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 12. Disaccharides 12B. Maltose Is a hydrolysis product from starch. Glucose (as an α-pyranose) Glucose (as an α-pyranose) © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 12. Disaccharides 12C. Cellobiose Is a hydrolysis product from cellulose. Glucose (as an α-pyranose) Glucose (as an α-pyranose) © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 12. Disaccharides 12D. Lactose Is present in mammalian milk. Galactose (as an α-pyranose) Glucose (as an α-pyranose) © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 13. Polysaccharides Polysaccharides are sugar units that are linked by glycosidic (acetal) bonds. Homopolysaccharides Are polymers with a single type of monosaccharide, With glucose monomeric units are glucans, and With galactose monomeric units are galactans. Heteropolysaccharides Are polymers containing more than one type of monosaccharide building block. © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 13. Polysaccharides 13A. Starch Is found in plants. Stores glucose for energy. All α-links. Amylose = Linear structure. Amylopectin = Branched structure. © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 13. Polysaccharides 13B. Glycogen Is found in animals. Stores glucose for energy. Has more α (1→6) branching than starch Branched structure only. All α-links. α-1,4 chains with α-1,6 branch points. © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 13. Polysaccharides 13C. Cellulose Is found in plants. Is a structural sugar. All β-links. Linear structure only. © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 14. Other Biologically Important Sugars Ribose and 2-Deoxyribose are Found in RNA and DNA respectively. Uronic Acids found in sulfonated polysaccharide called heparin. Heparin is important in controlling blood clotting. © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 15. Sugars that Contain Nitrogen 15A. Glycosamine Anomeric hydrogens are replaced by nitrogen. Nucleoside has Ribose and 2-Deoxyribose bonded to a nitrogenous ring system. © 2014 by John Wiley & Sons, Inc. All rights reserved.

© 2014 by John Wiley & Sons, Inc. All rights reserved. 15. Sugars that Contain Nitrogen 15B. Amino sugars have non-anomeric hydrogens replaced by nitrogen. β-D-glucosamine is found in chitin. NAG & NAM is found in bacterial cell walls. © 2014 by John Wiley & Sons, Inc. All rights reserved.

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