Textbook Question
Show how the substituents containing the azo group (N=N) can facilitate both electrophilic and nucleophilic aromatic substitution.
(a)
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Ch. 19 - Amines
Wade9th EditionOrganic ChemistryISBN: 9780135213728
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Table of contents
- Ch.1 - Structure and Bonding107
- Ch. 2 - Acids and Bases; Functional Groups115
- Ch.3 - Structure and Stereochemistry of Alkanes100
- Ch.4 - The Study of Chemical Reactions99
- Ch.5 - Stereochemistry93
- Ch.6 - Alkyl Halides; Nucleophilic Substitution118
- Ch. 7 - Structure and Synthesis of Alkenes; Elimination158
- Ch.8 - Reactions of Alkenes171
- Ch.9 - Alkynes91
- Ch.10 - Structure and Synthesis of Alcohols143
- Ch.11 - Reactions of Alcohols104
- Ch. 12 - Infrared Spectroscopy and Mass Spectrometry22
- Ch. 13 - Nuclear Magnetic Resonance Spectroscopy45
- Ch. 14 - Ethers, Epoxides, and Thioethers72
- Ch. 15 - Conjugated Systems, Orbital Symmetry, and Ultraviolet Spectroscopy89
- Ch. 16 - Aromatic Compounds74
- Ch. 17 - Reactions of Aromatic Compounds126
- Ch. 18 - Ketones and Aldehydes193
- Ch. 19 - Amines129
- Ch. 20 - Carboxylic Acids77
- Ch. 21 - Carboxylic Acid Derivatives141
- Ch. 22 - Condensations and Alpha Substitutions of Carbonyl Compounds175
- Ch. 23 - Carbohydrates and Nucleic Acids93
- Ch. 24 - Amino Acids, Peptides, and Proteins54
Chapter 19, Problem 65a,b
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 guidance1
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.
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Lactones and Lactams
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.
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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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Related Practice
Textbook Question
Reductive amination of aldehydes and ketones is a versatile method for attaching alkyl groups to amines, but the alkyl group is restricted to a 1° or 2° carbon by this method. Prof. Phil Baran of Scripps Research Institute has reported (Science, 2015, 348 (6237), 886–891) a novel way to reduce an aromatic nitro group and add the resulting amine to an alkene so that the aromatic amine is bonded to a 3° carbon—all in a continuous sequence of reactions.
For example:
Predict the products using these starting materials, all of which are reported in this paper.
(c)
(d)
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Textbook Question
Show how the substituents containing the azo group (N=N) can facilitate both electrophilic and nucleophilic aromatic substitution.
(b)
1
views
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.
(c) Identify the ketone in erythromycin targeted by bacteria as the site for detoxification.
(d) Identify the amine in azithromycin. What type of amine is it?
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