lithium methyl (4-methoxy-4-oxobutanoyl)phosphonate | 1220448-66-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: lithium methyl (4-methoxy-4-oxobutanoyl)phosphonate
• CAS: 1220448-66-7
• 化学式: C₆H₁₀O₆P*Li
• 分子量: 216.057
• InChiKey: GXCVZHCZSRUQER-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -3.33
• 重原子数：
  14.0
• 可旋转键数：
  5.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  92.73
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  丁二酸单甲酯 在 草酰氯 、 N,N-二甲基甲酰胺 、 lithium bromide 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 lithium methyl (4-methoxy-4-oxobutanoyl)phosphonate
  参考文献：
  名称：

  Succinylphosphonate Esters Are Competitive Inhibitors of MenD That Show Active-Site Discrimination between Homologous α-Ketoglutarate-Decarboxylating Enzymes

  摘要：

  MenD is a thiamin diphosphate-dependent enzyme catalyzing the First unique step in menaquinone biosynthesis in bacteria. We have synthesized acylphosphonate ester analogues of alpha-ketoglutarate, a substrate of MenD. These compounds are competitive inhibitors of MenD, with K-i values its low its 700 nM. Observed structure-activity relationships are in notable contrast to those reported previously for succinylphosphonate inhibition of the alpha-ketoglutarate dehydrogenase complex, despite the apparent homology of these enzymes, and the identical decarboxylation reactions catalyzed. Inhibiting menaquinone biosynthesis is it proposed approach to inhibiting Mycobacterium tuberculosis growth. These inhibitors showed no significant. inhibition of M. tuberculosis growth in vitro under aerobic and hypoxic conditions but give new information about the binding characteristics of the MenD active site. Site-directed Mutation of Ser391 to alanine had only it minor effect on catalysis, but even the conservative mutation of Arg395 to lysine had it significant effect on the catalytic processing of isochorismate.

  DOI：

  10.1021/bi901432d