A Scalable Synthesis of the Difluoromethyl-allo-threonyl Hydroxamate-Based LpxC Inhibitor LPC-058
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- 作者：Xiaofei Liang ; Ramesh Gopalaswamy ; Frank Navas III ; Eric J. Toone ; Pei Zhou
- 刊名：Journal of Organic Chemistry
- 出版年：2016
- 出版时间：May 20, 2016
- 年：2016
- 卷：81
- 期：10
- 页码：4393-4398
- 全文大小：420K
- 年卷期：0
- ISSN：1520-6904
文摘
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.