Abstract
The emerging global epidemic of drug-resistant tuberculosis has created an urgent need to identify novel therapeutic approaches for disease treatment. Transvalencin Z (1) is a natural product from Nocardia transvalensis with relatively potent and selective antimycobacterial activity against Mycobacterium smegmatis, making it an attractive target for structure-activity and mechanism of action studies. The total synthesis of the four possible diastereomers of transvalencin Z was completed (1a-d), and the absolute configurations were defined using chemical synthesis, HPLC retention times, and optical rotation measurements. Surprisingly, none of the transvalencin Z diastereomers exhibited any inhibitory activity against a panel of microbial pathogens, including several species of mycobacteria.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Acinetobacter baumannii / drug effects
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Animals
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Anti-Bacterial Agents / chemical synthesis*
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Anti-Bacterial Agents / chemistry
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Anti-Bacterial Agents / pharmacology*
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Bacillus subtilis / drug effects
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Candida albicans / drug effects
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Chlorocebus aethiops
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Chromatography, High Pressure Liquid
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Enterococcus faecalis / drug effects
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Escherichia coli / drug effects
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Klebsiella pneumoniae / drug effects
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Microbial Sensitivity Tests
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Molecular Structure
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Mycobacterium / drug effects
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Nocardia / chemistry
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Oxazoles / chemical synthesis*
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Oxazoles / chemistry
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Oxazoles / pharmacology*
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Pseudomonas aeruginosa / drug effects
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Salicylates / chemical synthesis*
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Salicylates / chemistry
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Salicylates / pharmacology*
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Staphylococcus aureus / drug effects
Substances
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Anti-Bacterial Agents
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Oxazoles
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Salicylates
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transvalencin Z