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A Scalable Synthesis of the Difluoromethyl-allo-threonyl Hydroxamate-Based LpxC Inhibitor LPC-058.

Publication ,  Journal Article
Liang, X; Gopalaswamy, R; Navas, F; Toone, EJ; Zhou, P
Published in: J Org Chem
May 20, 2016

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.

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Published In

J Org Chem

DOI

EISSN

1520-6904

Publication Date

May 20, 2016

Volume

81

Issue

10

Start / End Page

4393 / 4398

Location

United States

Related Subject Headings

  • Organic Chemistry
  • Molecular Conformation
  • Models, Molecular
  • Magnetic Resonance Spectroscopy
  • Indicators and Reagents
  • Gram-Negative Bacteria
  • Catalysis
  • Benzamides
  • Anti-Bacterial Agents
  • Amidohydrolases
 

Citation

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Liang, X., Gopalaswamy, R., Navas, F., Toone, E. J., & Zhou, P. (2016). A Scalable Synthesis of the Difluoromethyl-allo-threonyl Hydroxamate-Based LpxC Inhibitor LPC-058. J Org Chem, 81(10), 4393–4398. https://doi.org/10.1021/acs.joc.6b00589
Liang, Xiaofei, Ramesh Gopalaswamy, Frank Navas, Eric J. Toone, and Pei Zhou. “A Scalable Synthesis of the Difluoromethyl-allo-threonyl Hydroxamate-Based LpxC Inhibitor LPC-058.J Org Chem 81, no. 10 (May 20, 2016): 4393–98. https://doi.org/10.1021/acs.joc.6b00589.
Liang X, Gopalaswamy R, Navas F, Toone EJ, Zhou P. A Scalable Synthesis of the Difluoromethyl-allo-threonyl Hydroxamate-Based LpxC Inhibitor LPC-058. J Org Chem. 2016 May 20;81(10):4393–8.
Liang, Xiaofei, et al. “A Scalable Synthesis of the Difluoromethyl-allo-threonyl Hydroxamate-Based LpxC Inhibitor LPC-058.J Org Chem, vol. 81, no. 10, May 2016, pp. 4393–98. Pubmed, doi:10.1021/acs.joc.6b00589.
Liang X, Gopalaswamy R, Navas F, Toone EJ, Zhou P. A Scalable Synthesis of the Difluoromethyl-allo-threonyl Hydroxamate-Based LpxC Inhibitor LPC-058. J Org Chem. 2016 May 20;81(10):4393–4398.
Journal cover image

Published In

J Org Chem

DOI

EISSN

1520-6904

Publication Date

May 20, 2016

Volume

81

Issue

10

Start / End Page

4393 / 4398

Location

United States

Related Subject Headings

  • Organic Chemistry
  • Molecular Conformation
  • Models, Molecular
  • Magnetic Resonance Spectroscopy
  • Indicators and Reagents
  • Gram-Negative Bacteria
  • Catalysis
  • Benzamides
  • Anti-Bacterial Agents
  • Amidohydrolases