Table of contents

1. A Review of General Chemistry5h 5m
2. Molecular Representations1h 14m
3. Acids and Bases2h 46m
4. Alkanes and Cycloalkanes4h 17m
5. Chirality3h 39m
6. Thermodynamics and Kinetics1h 22m
7. Substitution Reactions1h 48m
8. Elimination Reactions2h 30m
9. Alkenes and Alkynes2h 9m
10. Addition Reactions3h 19m
11. Radical Reactions1h 58m
12. Alcohols, Ethers, Epoxides and Thiols2h 42m
13. Alcohols and Carbonyl Compounds2h 17m
14. Synthetic Techniques1h 26m
15. Analytical Techniques:IR, NMR, Mass Spect7h 3m
16. Conjugated Systems6h 13m
17. Ultraviolet Spectroscopy51m
18. Aromaticity2h 34m
19. Reactions of Aromatics: EAS and Beyond5h 1m
20. Phenols55m
21. Aldehydes and Ketones: Nucleophilic Addition4h 56m
22. Carboxylic Acid Derivatives: NAS2h 51m
23. The Chemistry of Thioesters, Phophate Ester and Phosphate Anhydrides1h 10m
24. Enolate Chemistry: Reactions at the Alpha-Carbon1h 53m
25. Condensation Chemistry2h 9m
26. Amines1h 43m
27. Heterocycles2h 0m
28. Carbohydrates5h 53m
29. Amino Acids4h 20m
30. Peptides and Proteins2h 42m
31. Catalysis in Organic Reactions1h 30m
32. Lipids 2h 50m
33. The Organic Chemistry of Metabolic Pathways2h 52m
34. Nucleic Acids1h 32m
35. Transition Metals6h 14m
36. Synthetic Polymers1h 49m

22. Carboxylic Acid Derivatives: NAS

Lactones, Lactams and Cyclization Reactions

Organic Chemistry

22. Carboxylic Acid Derivatives: NAS

Lactones, Lactams and Cyclization Reactions

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5:42 minutes

Problem 65a,b

Textbook Question

Macrolide antibiotics all have large rings (macrocycle) in which an ester makes the ring; a cyclic ester is termed a lactone. One example is erythromycin A, first isolated from soil bacteria in the 1950s. Over time, some pathogenic bacteria have developed resistance to erythromycin by evolving an enzymatic mechanism to cleave the macrocycle at the ketone. To counter this resistance, chemists modified the erythromycin structure to replace the ketone with an amine that the bacteria could not detoxify. This modified antibiotic, azithromycin, trade name Zithromax®, is one of the most prescribed drugs in the world for respiratory infections.

(a) Identify the lactone group in each structure that merits the classification as macrolides.
(b) Two groups are circled. What type of functional group are they? Explain.

Verified step by step guidance

Identify the lactone group in erythromycin A: Look for a large ring structure that contains an ester linkage. In erythromycin A, the lactone group is the 14-membered ring containing an ester bond, which is characterized by the carbonyl group (C=O) adjacent to an oxygen atom within the ring.

Identify the lactone group in azithromycin: Similarly, in azithromycin, the lactone group is also a 15-membered ring with an ester linkage. The presence of the nitrogen atom in the ring differentiates it from erythromycin A, but the ester linkage is still present.

Examine the circled groups in erythromycin A: The circled groups in the structure are sugar moieties attached to the macrolide ring. These are glycosidic linkages, which are characterized by an oxygen atom connecting the sugar to the macrolide ring.

Examine the circled groups in azithromycin: The circled groups in azithromycin are also sugar moieties. These are similar to those in erythromycin A, with glycosidic linkages connecting the sugars to the macrolide ring.

Explain the functional groups: The circled groups are glycosidic linkages, which are a type of acetal linkage formed between a sugar and another molecule. These linkages are important for the biological activity of macrolide antibiotics, as they help in binding to bacterial ribosomes.

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Key Concepts

Here are the essential concepts you must grasp in order to answer the question correctly.

Lactone Group

A lactone is a cyclic ester that forms when a hydroxyl group and a carboxylic acid group within the same molecule react, releasing a molecule of water. In macrolide antibiotics like erythromycin A and azithromycin, the lactone group is part of a large ring structure, which is crucial for their biological activity. The lactone ring is typically a 12- to 16-membered ring, contributing to the classification of these compounds as macrolides.

Functional Groups

Functional groups are specific groups of atoms within molecules that are responsible for the characteristic chemical reactions of those molecules. In the provided structures, the circled groups are likely to be amines or other nitrogen-containing groups, which are significant in altering the drug's properties. For azithromycin, the modification from a ketone to an amine group is crucial for overcoming bacterial resistance by preventing enzymatic cleavage of the macrocycle.

Macrolide Antibiotics

Macrolides are a class of antibiotics characterized by their large macrocyclic lactone rings. They function by inhibiting bacterial protein synthesis, making them effective against a variety of bacterial infections. Erythromycin A and azithromycin are examples, with azithromycin being a modified version designed to overcome bacterial resistance by replacing a ketone group with an amine, enhancing its efficacy and stability against enzymatic degradation.

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