Abstract
Nocathiacin I (1) and nocathiacin IV (2) are novel indole-containing thiazolyl peptide antibiotics, which exhibit potent activity against key Gram-positive bacterial pathogens, including multi drug-resistant Staphylococcus aureus, Streptococcus pneumoniae, and Enterococcus faecium. New nocathiacins 7-12 were prepared from 2 by a condensation with glycolaldehyde followed by tandem reductive amination of the 2-oxoethyl intermediate 4. The latter was formed via Amadori rearrangement from initial 2-hydroxyethylideneamide 3. This transformation readily tolerates the complex architecture of nocathiacins and allows selective incorporation of water solubilizing groups to the primary amide in 2 without protecting group manipulation.
MeSH terms
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Acetaldehyde / analogs & derivatives*
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Acetaldehyde / chemistry*
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Amides / chemistry
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Anti-Bacterial Agents / chemical synthesis*
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Anti-Bacterial Agents / pharmacology
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Catalysis
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Combinatorial Chemistry Techniques*
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Drug Resistance, Multiple, Bacterial
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Enterococcus faecium / drug effects
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Intercellular Signaling Peptides and Proteins
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Microbial Sensitivity Tests
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Molecular Structure
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Peptides*
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Peptides, Cyclic / chemical synthesis*
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Peptides, Cyclic / pharmacology
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Staphylococcus aureus / drug effects
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Streptococcus pneumoniae / drug effects
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Structure-Activity Relationship
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Thiazoles / chemical synthesis*
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Thiazoles / pharmacology
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Water / chemistry
Substances
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Amides
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Anti-Bacterial Agents
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Intercellular Signaling Peptides and Proteins
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Peptides
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Peptides, Cyclic
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Thiazoles
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nocathiacin I
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nocathiacin IV
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Water
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Acetaldehyde
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glycolaldehyde