Abstract
The synthesis of 6-O-methyl-azithromycin and its aza-ketolide analogue have been achieved by carrying out the Beckmann rearrangement of the readily available 9(E)-6-O-methyl-erythromycin oxime 1. In contrast to the C14 ketolides like HMR 3647, the aza-ketolide turns out to be inactive, thus demonstrating that the addition of a 3 keto function and ring expansion, from 14 to 15 membered ring, could be deleterious for the antibacterial activity.
MeSH terms
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Anti-Bacterial Agents / chemistry*
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Anti-Bacterial Agents / pharmacology
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Azithromycin / analogs & derivatives*
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Azithromycin / pharmacology
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Erythromycin / analogs & derivatives*
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Erythromycin / pharmacology
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Escherichia coli / drug effects
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Haemophilus influenzae / drug effects
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Ketolides*
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Macrolides*
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Microbial Sensitivity Tests
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Models, Molecular
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Staphylococcus aureus / drug effects
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Streptococcus / drug effects
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Structure-Activity Relationship
Substances
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Anti-Bacterial Agents
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Ketolides
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Macrolides
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Erythromycin
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Azithromycin
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telithromycin