Abstract
The difluoromethyl-allo-threonyl hydroxamate-based compound LPC-058 is a potent inhibitor of UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC) in Gram-negative bacteria. A scalable synthesis of this compound is described. The key step in the synthetic sequence is a transition metal/base-catalyzed aldol reaction of methyl isocyanoacetate and difluoroacetone, giving rise to 4-(methoxycarbonyl)-5,5-disubstituted 2-oxazoline. A simple NMR-based determination of enantiomeric purity is also described.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Amidohydrolases / antagonists & inhibitors*
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Anti-Bacterial Agents / chemical synthesis*
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Anti-Bacterial Agents / pharmacology*
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Benzamides / chemical synthesis*
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Benzamides / pharmacology*
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Catalysis
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Gram-Negative Bacteria / drug effects
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Gram-Negative Bacteria / enzymology
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Indicators and Reagents
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Magnetic Resonance Spectroscopy
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Models, Molecular
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Molecular Conformation
Substances
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Anti-Bacterial Agents
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Benzamides
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Indicators and Reagents
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LPC-058
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Amidohydrolases
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UDP-3-O-acyl-N-acetylglucosamine deacetylase