2-[(1-Amino-ethyl)-methoxy-phosphinoylmethyl]-pentanedioic acid dimethyl ester | 874156-89-5

• 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: 2-[(1-Amino-ethyl)-methoxy-phosphinoylmethyl]-pentanedioic acid dimethyl ester
• 英文别名: Dimethyl 2-[[1-aminoethyl(methoxy)phosphoryl]methyl]pentanedioate
• CAS: 874156-89-5
• 化学式: C₁₁H₂₂NO₆P
• 分子量: 295.273
• InChiKey: XLVIJAXZHBSZET-UHFFFAOYSA-N

物化性质

• 沸点：
  372.6±52.0 °C(Predicted)
• 密度：
  1.171±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  19
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-[(1-Amino-ethyl)-methoxy-phosphinoylmethyl]-pentanedioic acid dimethyl ester 在 platinum(IV) oxide sodium hydroxide 、 三辛胺 、 AG 50W-X₈ 、 氢气 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 119.0h， 生成 {1-[(6-uridinediphospho)hexanamido]ethyl}(2,4-dicarboxybutyl)phosphinate pentasodium salt
  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 作用下， 以 甲醇 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 15.25h， 生成 2-[(1-Amino-ethyl)-methoxy-phosphinoylmethyl]-pentanedioic acid dimethyl ester
  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

• Design, synthesis and structure–activity relationships of new phosphinate inhibitors of MurD
  作者：Katja Štrancar、Didier Blanot、Stanislav Gobec

  DOI：10.1016/j.bmcl.2005.09.086

  日期：2006.1

  A series of new phosphinate compounds were designed and synthesized as inhibitors of the D-glutamic acid-adding enzyme (MurD) involved in peptidoglycan biosynthesis. They were tested against the MurD enzyme from Escherichia coli, allowing initial structure-activity relationships to be deduced. Two compounds had IC50 values near 100 mu M and constitute a promising starting point for further development. (c) 2005 Elsevier Ltd. All rights reserved.
• 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.