IspC as Target for Antiinfective Drug Discovery: Synthesis, Enantiomeric Separation, and Structural Biology of Fosmidomycin Thia Isosters
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- 作者：Andrea Kunfermann ; Claudia Lienau ; Boris Illarionov ; Jana Held ; Tobias Gr盲wert ; Christoph T. Behrendt ; Philipp Werner ; Saskia H盲hn ; Wolfgang Eisenreich ; Ulrich Riederer ; Benjamin Mordm眉ller ; Adelbert Bacher ; Markus Fischer ; Michael Groll ; Thomas Kurz
- 刊名：Journal of Medicinal Chemistry
- 出版年：2013
- 出版时间：October 24, 2013
- 年：2013
- 卷：56
- 期：20
- 页码：8151-8162
- 全文大小：599K
- 年卷期：v.56,no.20(October 24, 2013)
- ISSN：1520-4804
文摘
The emergence and spread of multidrug-resistant pathogens are widely believed to endanger human health. New drug targets and lead compounds exempt from cross-resistance with existing drugs are urgently needed. We report on the synthesis and properties of 鈥渞everse鈥?thia analogs of fosmidomycin, which inhibit the first committed enzyme of a metabolic pathway that is essential for the causative agents of tuberculosis and malaria but is absent in the human host. Notably, IspC displays a high level of enantioselectivity for an 伪-substituted fosmidomycin derivative.