methyl <1-acetamidoethyl>(2,4-dicarbomethoxybutyl)phosphinate | 174280-82-1

• 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: methyl <1-acetamidoethyl>(2,4-dicarbomethoxybutyl)phosphinate
• 英文别名: Dimethyl 2-[[1-acetamidoethyl(methoxy)phosphoryl]methyl]pentanedioate
• CAS: 174280-82-1
• 化学式: C₁₃H₂₄NO₇P
• 分子量: 337.31
• InChiKey: XLAGIEVVHWUAOL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  22
• 可旋转键数：
  11
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  108
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl <1-acetamidoethyl>(2,4-dicarbomethoxybutyl)phosphinate 在 sodium hydroxide 作用下， 以 水 为溶剂， 反应 3.0h， 以99%的产率得到(1-acetamidoethyl)(2,4-dicarboxybutyl)phosphinic acid
  参考文献：
  名称：

  Phosphinate Inhibitors of the d-Glutamic Acid-Adding Enzyme of Peptidoglycan Biosynthesis

  摘要：

  We report the synthesis and initial evaluation of the first effective inhibitors of the D-glutamic acid-adding enzyme (UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase or MurD). This enzyme plays a key role in bacterial peptidoglycan biosynthesis and is therefore a target for antibiotic design. Phosphinic acid 3 is a dipeptide analog linked to uridine diphosphate by a hydrophobic spacer. It is a good inhibitor of the enzyme (IC50 = 0.68 mu M) as it closely resembles the tetrahedral intermediate that is presumed to form in the ligation reaction. Compound 4 lacks the terminal UMP group, and compound 5 lacks both the linker and UDP functionalities. These are less effective inhibitors of the enzyme with IC50 values of 29 mu M and > 1 mM, respectively. Preincubation of the enzyme in the presence of inhibitor 3 and ATP does not result in irreversible inhibition or in the formation of a slowly decomplexing species, suggesting that the phosphinic acid is not phosphorylated in the active site.

  DOI：

  10.1021/jo951780a
• 作为产物：
  描述：

  2-亚甲基戊二酸二甲酯 在 palladium on activated charcoal 氢气 、 sodium methylate 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 17.25h， 生成 methyl <1-acetamidoethyl>(2,4-dicarbomethoxybutyl)phosphinate
  参考文献：
  名称：

  Phosphinate Inhibitors of the d-Glutamic Acid-Adding Enzyme of Peptidoglycan Biosynthesis

  摘要：

  We report the synthesis and initial evaluation of the first effective inhibitors of the D-glutamic acid-adding enzyme (UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase or MurD). This enzyme plays a key role in bacterial peptidoglycan biosynthesis and is therefore a target for antibiotic design. Phosphinic acid 3 is a dipeptide analog linked to uridine diphosphate by a hydrophobic spacer. It is a good inhibitor of the enzyme (IC50 = 0.68 mu M) as it closely resembles the tetrahedral intermediate that is presumed to form in the ligation reaction. Compound 4 lacks the terminal UMP group, and compound 5 lacks both the linker and UDP functionalities. These are less effective inhibitors of the enzyme with IC50 values of 29 mu M and > 1 mM, respectively. Preincubation of the enzyme in the presence of inhibitor 3 and ATP does not result in irreversible inhibition or in the formation of a slowly decomplexing species, suggesting that the phosphinic acid is not phosphorylated in the active site.

  DOI：

  10.1021/jo951780a

文献信息

• Phosphinate Inhibitors of the <scp>d</scp>-Glutamic Acid-Adding Enzyme of Peptidoglycan Biosynthesis
  作者：Martin E. Tanner、Sabine Vaganay、Jean van Heijenoort、Didier Blanot

  DOI：10.1021/jo951780a

  日期：1996.1.1

  We report the synthesis and initial evaluation of the first effective inhibitors of the D-glutamic acid-adding enzyme (UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase or MurD). This enzyme plays a key role in bacterial peptidoglycan biosynthesis and is therefore a target for antibiotic design. Phosphinic acid 3 is a dipeptide analog linked to uridine diphosphate by a hydrophobic spacer. It is a good inhibitor of the enzyme (IC50 = 0.68 mu M) as it closely resembles the tetrahedral intermediate that is presumed to form in the ligation reaction. Compound 4 lacks the terminal UMP group, and compound 5 lacks both the linker and UDP functionalities. These are less effective inhibitors of the enzyme with IC50 values of 29 mu M and > 1 mM, respectively. Preincubation of the enzyme in the presence of inhibitor 3 and ATP does not result in irreversible inhibition or in the formation of a slowly decomplexing species, suggesting that the phosphinic acid is not phosphorylated in the active site.