Chapter 32 — Exercises

Fifty-five problems on carbohydrate structure, reactivity, and biology. Drawing required wherever a structure or mechanism is asked for. ∗ marks problems with full worked solutions in Appendix Answers to Selected Exercises.

Section A — Structure and classification

32.1∗ (routine) Classify each as aldose or ketose, and by carbon count: (a) glucose (b) fructose (c) ribose (d) galactose (e) erythrose (f) sedoheptulose

32.2 (routine) Draw D-glucose in Fischer projection. Identify each stereocenter and assign (R)/(S). Confirm that C5 has the OH on the right (the D-configuration).

32.3∗ (routine) Draw the open-chain Fischer projection of: (a) D-mannose (C2 epimer of glucose) (b) D-galactose (C4 epimer of glucose) (c) D-fructose (the 2-keto isomer)

32.4 (routine) Why are L-sugars rare in biology? What is the molecular reason?

32.5 (moderate) A pentaldose has 3 stereocenters. How many possible D-pentaldoses are there? Name them.

32.6 (challenge) A heptaldose has 5 stereocenters. How many possible D-heptaldoses are there? (Calculate the binomial.)

Section B — Cyclic forms and anomers

32.7∗ (routine) Draw α-D-glucopyranose and β-D-glucopyranose in chair form. Identify the axial vs. equatorial position of each substituent.

32.8 (routine) Draw α- and β-D-fructofuranose. Identify the anomeric carbon (C2, not C1, since fructose is a ketose).

32.9∗ (routine) Mutarotation: starting with pure α-D-glucopyranose in water, the optical rotation changes from [α] = +112° to +52.7° over time. Why? Sketch the equilibrium and the path.

32.10 (routine) What percent of D-glucose is in: (a) α-pyranose, (b) β-pyranose, (c) open-chain, (d) furanose forms in water at 25 °C? Why is β preferred?

32.11 (moderate) Draw the chair conformation of α-D-glucopyranose. Why is β preferred over α (give two reasons: steric + electronic)?

32.12 (moderate) The anomeric effect: the α-anomer is more stable than purely steric arguments would predict. Sketch the n→σ* hyperconjugation that gives this effect. Why does it stabilize the axial OH?

32.13 (challenge) D-mannose's α/β equilibrium is 67% α : 33% β. Why is this opposite to glucose's? Hint: think about the C2-OH orientation.

Section C — Reactions of monosaccharides

32.14∗ (routine) Predict the product: (a) D-glucose + NaBH₄ → ? (b) D-glucose + Br₂/H₂O → ? (c) D-glucose + 5 acetic anhydride → ? (d) D-glucose + HNO₃/dilute → ?

32.15 (routine) Predict the products of glycoside formation: D-glucose + methanol + H⁺ → ?

32.16 (moderate) Draw the mechanism of glycoside formation from D-glucose + methanol + H⁺. Include the oxocarbenium intermediate.

32.17 (moderate) Identify whether each is a reducing sugar: (a) glucose (b) sucrose (c) lactose (d) maltose (e) cellobiose (f) fructose

32.18 (moderate) A reducing sugar tests positive with Tollens' reagent (gives a silver mirror) or Fehling's solution (gives red Cu₂O precipitate). Both are mild oxidants. Sketch the mechanism: aldose's anomeric C is in equilibrium with the open-chain CHO; CHO is oxidized to COOH.

32.19 (challenge) Periodic acid cleavage of D-mannitol (the polyol from glucose reduction): predict the products. How many molecules of formaldehyde, formic acid, and HCHO are formed?

32.20 (challenge) A student is asked to make ethyl β-D-glucopyranoside selectively. Suggest conditions to favor the β over the α anomer in the glycosylation.

Section D — Disaccharides

32.21∗ (routine) Draw the structures of: (a) maltose (α-1,4-glucose-glucose) (b) lactose (β-1,4-galactose-glucose) (c) sucrose (α-1,β-2-glucose-fructose)

32.22 (routine) Identify the glycosidic linkage type (α/β, 1,4 or other) in each: (a) maltose (b) cellobiose (the disaccharide of cellulose) (c) lactose (d) sucrose

32.23 (moderate) Why is sucrose a non-reducing sugar but lactose is reducing?

32.24 (moderate) Why does maltose have free anomeric OH (and thus is reducing) but sucrose does not? Look at the structure carefully.

32.25 (challenge) Lactose intolerance: explain the molecular basis. What enzyme is deficient? What happens to undigested lactose?

32.26 (challenge) Design an enzymatic synthesis of lactose from glucose + galactose. What enzyme would you need? What is the activated donor?

Section E — Polysaccharides

32.27∗ (routine) Predict the structural and biological consequences of: (a) α-1,4 glucose backbone (starch) (b) β-1,4 glucose backbone (cellulose) Why is starch helical and digestible while cellulose is linear and indigestible?

32.28 (routine) Glycogen is highly branched (α-1,4 + α-1,6). Why is this advantageous for an animal storing glucose?

32.29 (moderate) Cellulose's β-1,4 linkage forces the chain to alternate orientation at each glucose. Sketch this and explain why it gives a flat, ribbon-like structure suitable for hydrogen-bonded fiber formation.

32.30 (moderate) Chitin is β-1,4 N-acetylglucosamine. Why is chitin similar to cellulose in physical properties? What is its biological role?

32.31 (challenge) Hyaluronic acid is alternating glucuronic acid + N-acetylglucosamine. Why is HA so highly hydrated, and what is its biological role in joints?

32.32 (challenge) Cellulose is the most abundant biopolymer on Earth (~50% of biomass). What is the next most abundant? (Answer: chitin.) Why are these particular structures so common?

Section F — Biology and metabolism

32.33∗ (routine) Identify the carbonyl chemistry in: (a) glycolytic aldolase reaction (retro-aldol), (b) pyruvate kinase (enol-keto tautomerism), (c) glucose-6-phosphate isomerase (aldose-ketose isomerization).

32.34 (routine) A glycolytic intermediate, fructose-1,6-bisphosphate, is cleaved by aldolase. What are the products? Identify the retro-aldol mechanism.

32.35 (moderate) Glycogen breakdown by glycogen phosphorylase yields glucose-1-phosphate, not glucose. Why is this advantageous for cell metabolism?

32.36 (moderate) Describe the chemistry of glucose-6-phosphate dehydrogenase (the rate-limiting step of the pentose phosphate pathway). What is the product?

32.37 (moderate) HbA1c (glycated hemoglobin) is the imine of glucose's C1 + N-terminal valine of hemoglobin, after Amadori rearrangement. Sketch the chemistry: imine + α-H removal + protonation + ring opening = Amadori product.

32.38 (challenge) A diabetic patient has HbA1c = 7.5%. Estimate their average blood glucose over the past 3 months. (Hint: HbA1c% × 28.7 - 46.7 ≈ avg glucose mg/dL.)

Section G — Glycoproteins and cell biology

32.39∗ (routine) A glycoprotein has an N-linked glycan (attached via amide nitrogen of asparagine). Sketch the glycan-protein bond. What is the typical core structure?

32.40 (routine) Influenza hemagglutinin binds sialic acid on cell surface glycoproteins. Sketch sialic acid (N-acetylneuraminic acid) and identify the carbonyl chemistry that distinguishes it from glucose.

32.41 (moderate) Blood types A, B, and O differ by the presence or absence of specific sugars on red blood cell glycoproteins. Identify which sugar is added in: (a) blood type A, (b) blood type B, (c) blood type O.

32.42 (moderate) Why do blood transfusions need to match blood type? What is the molecular reason?

32.43 (challenge) A "universal donor" blood type would be useful clinically. Discuss enzymatic strategies to convert type A or B blood to type O.

Section H — Spectroscopy and analytics

32.44∗ (routine) A monosaccharide is dissolved in water and the optical rotation is measured at +18.7°. After 24 hours, the rotation has reached +52.7°. Identify the starting compound and explain.

32.45 (routine) ¹H NMR of α- vs β-anomeric glucose: the α-H1 is at δ 5.2 (J = 3 Hz); the β-H1 is at δ 4.6 (J = 7 Hz). Explain the chemical shift difference and the coupling constant difference.

32.46 (moderate) ¹³C NMR of glucose anomeric C: α at δ 93; β at δ 97. Explain the small difference.

32.47 (challenge) Mass spectrum of D-glucose: M⁺ at 180. Major fragment at 144 (loss of 2 H₂O). Sketch the fragmentation.

Section I — Multistep synthesis

32.48 (routine) Design a synthesis of methyl α-D-glucopyranoside from D-glucose + methanol + acid.

32.49 (moderate) Design a synthesis of D-glucose pentaacetate (all 5 OH groups acetylated). Identify any selectivity considerations.

32.50 (moderate) Design a synthesis of D-glucitol (sorbitol) from D-glucose. What is the reagent?

32.51 (challenge) Design a synthesis of a disaccharide (e.g., methyl α-D-glucopyranosyl-(1→4)-β-D-glucopyranoside) using protecting groups and selective glycosylation.

32.52 (challenge) Outline the chemistry of glycoprotein synthesis in the endoplasmic reticulum. What is the activated donor (UDP-sugar)? What is the mechanism of glycosyltransferase?

Section J — Industrial and applied

32.53 (challenge) Sucralose (Splenda) is a tri-chlorinated sucrose derivative. Sketch the structure. Why is it ~600× sweeter than sucrose? Why is it not metabolized by humans?

32.54 (challenge) Aspartame (a non-sugar sweetener, but related to sugar chemistry indirectly) is the methyl ester of an aspartate-phenylalanine dipeptide. Sketch its structure. Why is it sweet?

32.55 (challenge) Cellulose-based bioplastics (e.g., cellophane, viscose rayon) are made by chemical modification of cellulose. Outline the process: dissolve cellulose, modify, regenerate. Why is this commercially significant?

Notes for instructors: Common stumbling blocks for Chapter 32: (1) Confusing Fischer (open-chain) and Haworth/chair (cyclic) drawings. (2) Mistaking α/β anomeric configuration. (3) Forgetting the role of the open-chain form in mutarotation and reducing sugars. (4) Confusing cellulose's β-1,4 vs. starch's α-1,4 linkages. Computational exercises: optimize α- and β-D-glucopyranose chairs in Avogadro; compare relative energies (β should be lower by ~0.7 kcal/mol).