Organic Chemistry Second Edition Chapter 24 David Klein Carbohydrates Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.1 Introduction to Carbohydrates Carbohydrates (sugars) are abundant in nature High energy biomolecules Provide structural rigidity for organisms (plants, crustaceans, etc.) The polymer backbone on which DNA and RNA are assembled Expressed on cells so they can recognize one another The term, carbohydrate, evolved to describe the formula for such molecules: Cx(H2O)x Carbohydrates are NOT true hydrates. WHY? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.1 Introduction to Carbohydrates Carbohydrates (sugars) are polyhydroxy aldehydes or ketones Consider glucose, which is made by plants Describe the potential energy change that occurs during glucose photosynthesis Is glucose a polyhydroxy aldehyde or ketone? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.2 Classification of Monosaccharides Saccharides have multiple chiral centers, and they are often expressed as Fischer projections checkpoints 24.1 and 24.2 What does the suffix, “ose” mean? Define the following terms: Aldose and ketose Pentose and hexose Practice conceptual Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Klein, Organic Chemistry 2e Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.2 Classification of Monosaccharides Glyceraldehyde is a monosaccharide with one chirality center Natural glyceraldehyde is dextrorotatory (D) – it rotates plane polarized light in the clockwise direction Does the direction plane polarized light is rotated necessarily tell us whether it is (R) or (S)? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.2 Classification of Monosaccharides Naturally occurring larger sugars can be broken down into glyceraldehyde by degradation Such sugars are often called D sugars Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.2 Classification of Monosaccharides Recall that dextrorotatory versus levorotatory rotation can not be predicted by the R or S configuration Practice conceptual checkpoints 24.3 through 24.6 Here, D no longer refers to dextrorotatory. Rather it refers to the R configuration at the chiral carbon farthest from the carbonyl Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Klein, Organic Chemistry 2e Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.3 Configuration of Aldoses There are four aldotetroses. Two are shown below What are the other two structures? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.3 Configuration of Aldoses Aldopentoses have three chirality centers. The number of isomers will be 23 Recall the 2n rule from section 5.5 The D sugars are naturally occurring Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.3 Configuration of Aldoses Ribose is a key building block of RNA WHAT is RNA? More detail to come in section 24.10 Arabinose is found in plants Xylose is found in wood Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.3 Configuration of Aldoses Based on the 2n rule, how many aldohexoses are there? How many of the aldohexoses are D isomers Glucose is the most common aldohexose Manose and Galactose are also common Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.4 Configuration of Ketoses Relevant ketoses have between 3 and 6 carbons For each naturally occurring D isomer, there is an L enantiomer Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.4 Configuration of Ketoses Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.5 Cyclic Structures of Monosaccharides Recall from section 20.5 that carbonyls can be attacked by alcohols to form hemiacetals The intermolecular reaction is not favored. WHY? The intramolecular reaction is generally favored for 5 and 6-membered rings. WHY? Practice with SkillBuilder 24.1 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Klein, Organic Chemistry 2e Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.5 Cyclic Structures of Monosaccharides Monosaccharides like glucose can also undergo ring-closing hemiacetal formation The equilibrium greatly favors the closed form called pyranose Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.5 Cyclic Structures of Monosaccharides What is the relationship between alpha and beta forms? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.5 Cyclic Structures of Monosaccharides Distinguish between the α and β anomers [a]D = +112.2˚ [a]D = +18.7˚ Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.5 Cyclic Structures of Monosaccharides You should be able to draw monosaccharide structures in their various forms Practice with SkillBuilder 24.3 Draw the chair form D-Galactose Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Klein, Organic Chemistry 2e Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Klein, Organic Chemistry 2e Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Klein, Organic Chemistry 2e Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.5 Cyclic Structures of Monosaccharides Ketoses form both furanose (5-membered) and pyranose (6-membered) rings Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.5 Cyclic Structures of Monosaccharides The furanose form takes part in most biochemical reactions Practice with conceptual checkpoints 24.22 through 24.25 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.6 Reactions of Monosaccharides Monosaccharides are generally soluble in water. WHY? To improve their solubility in organic solvents, the hydroxyl groups can be acetylated WHY is pyridine added to the reaction? How might acetylation help in purification efforts? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.6 Reactions of Monosaccharides Monosaccharides can also be converted to ethers via the Williamson ether synthesis Ether linkages are more robust than ester linkages. WHY? Practice with conceptual checkpoints 24.26 and 24.27 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.6 Reactions of Monosaccharides When treated with an excess of an alcohol, the hemiacetal equilibrium can be shifted to give an acetal When a sugar is used, alpha and beta glycosides are formed Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.6 Reactions of Monosaccharides The mechanism of glycoside formation is analogous to the acetal formation mechanism Only the anomeric hydroxyl group is replaced Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.6 Reactions of Monosaccharides The mechanism of glycoside formation is analogous to the acetal formation mechanism Practice with conceptual checkpoints 24.28 and 24.29 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Klein, Organic Chemistry 2e Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.6 Reactions of Monosaccharides Under strongly basic conditions, glucose and mannose interconvert Mannose and glucose are epimers, because they only differ in the configuration of one carbon center Practice with conceptual checkpoint 24.30 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Klein, Organic Chemistry 2e Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.6 Reactions of Monosaccharides Monosaccharides can be reduced to alditols shifting the equilibrium to the right. HOW? D-sorbitol or D-glucitol are sugar substitutes Practice with checkpoints24.31 through 24.33 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.6 Reactions of Monosaccharides A monosaccharide can also be oxidized using a variety of oxidizing agents including Br2 to form a aldonic acid A mild oxidizing agent must be used to avoid oxidation of the alcohol groups Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.6 Reactions of Monosaccharides Practice with SkillBuilder 24.4 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.6 Reactions of Monosaccharides HCN can react with sugars to produce cyanohydrins In the original Kiliani-Fischer synthesis, the cyanohydrin is subsequently converted to an acid and then an aldehyde extending the carbon chain by one unit Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.6 Reactions of Monosaccharides A more recent version of the Kiliani-Fischer synthesis converts the cyanohydrin to the aldehyde in one step Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.6 Reactions of Monosaccharides A more recent version of the Kiliani-Fischer synthesis converts the cyanohydrin to the aldehyde in one step Practice with conceptual checkpoints 24.37 and 24.38 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.6 Reactions of Monosaccharides Although it is not very high yielding, the Wohl synthesis achieves the reverse of the Kiliani-Fischer synthesis Practice with conceptual checkpoints 24.39 through 24.41 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Klein, Organic Chemistry 2e Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.7 Disaccharides Disaccharides form when two sugars connect through a glycosidic linkage Because the anomeric position of the bottom ring is a HEMIacetal rather than an acetal, it is in equilibrium with the open form. Thus, maltose is a reducing sugar Practice with SkillBuilder 24.5 The 1  4 glycosidic linkage is most common The bottom ring is capable of maturotation at its anomeric position Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.7 Disaccharides Cellobiose is similar to maltose. WHAT are the differences? Will cellobiose be a reducing sugar? Practice conceptual checkpoint 24.44 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Klein, Organic Chemistry 2e Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Klein, Organic Chemistry 2e Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Klein, Organic Chemistry 2e Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.7 Disaccharides Lactose is another disaccharide Some people have trouble digesting lactose. WHY? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.7 Disaccharides Sucrose (table sugar) is also a disaccharide Honey bees can convert sucrose into a mixture of sucrose, fructose, and glucose Fructose is very sweet Sucrose is not a reducing sugar. WHY? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.8 Polysaccharides Cellulose is a polysaccharide containing 7000-12000 glucose units connected through glycosidic bonds How is cellulose capable of giving plants like trees their rigidity and strength? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.8 Polysaccharides Starch is a major components of grains and other foods like potatoes Starch is made of amylose and amylopectin What is the difference between molecules of starch and molecules of cellulose? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.8 Polysaccharides Amylopectin has some 16-α-glycoside branches We can eat corn and potatoes, but not grass or trees. WHY? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.9 Amino Sugars Amino sugars like glucosamine are important biomolecules Acetylated glucosamine can form an important polysaccharide called chitin Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.9 Amino Sugars The carbonyl groups in chitin allow for even stronger H-bonding between neighboring chains Chitin is used in insect and arthropod exoskeletons. WHY? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.10 N-Glycosides N-glycosides can be formed when sugars are treated with an amine and an acid catalyst RNA and DNA incorporate important N-glycosides called nucleosides Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.10 N-Glycosides Ribose forms ribonucleosides in RNA Deoxyribose forms deoxyribonucleosides in DNA Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.10 N-Glycosides There are 4 different heterocyclic amines that attach to deoxyribose molecules to form DNA nucleosides Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.10 N-Glycosides In DNA, the nucleosides are attached to phosphate groups forming nucleotides Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.10 N-Glycosides The phosphate groups of the nucleotides are connected together to make the DNA strand or polynucleotide Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.10 N-Glycosides The nucleotides in DNA can attract one another through H-bonding of the DNA base pairs Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.10 N-Glycosides WHY does DNA form a double helix? Consider both H-bonding and pi stacking of the base pairs Consider ion-dipole interactions with the solvent Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.10 N-Glycosides RNA is structurally different from DNA The sugar in RNA is ribose. WHAT is the sugar in DNA? RNA contains the uracil instead of thymine RNA translates the information stored in DNA into working molecules (proteins and enzymes) Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

24.10 N-Glycosides RNA strands generally do not form the double helix like DNA RNA strands can fold into many different shapes, and some even act as catalysts called ribozymes It is possible that RNA evolved self-replication as an early step in the evolution of life from small molecules Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Additional Practice Problems How does the potential energy of carbohydrates and O2 compare with the potential energy state of CO2 and H2O, and how do carbohydrates provide an energy source? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Additional Practice Problems Explain why the equilibrium for ring formation in pentoses and hexoses favors the ring rather than the open form. Is your argument kinetic or thermodynamic? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Additional Practice Problems Predict the product of a sugar reacting with an amine and give the mechanism for formation. Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Additional Practice Problems Which of the molecules discussed in this chapter could accurately be classified as polymers? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e