2-({1-[6-(Diphenoxy-phosphoryloxy)-hexanoylamino]-ethyl}-methoxy-phosphinoylmethyl)-pentanedioic acid dimethyl ester | 174280-83-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磷酸及其衍生物
• 英文名称: 2-({1-[6-(Diphenoxy-phosphoryloxy)-hexanoylamino]-ethyl}-methoxy-phosphinoylmethyl)-pentanedioic acid dimethyl ester
• 英文别名: Dimethyl 2-[[1-(6-diphenoxyphosphoryloxyhexanoylamino)ethyl-methoxyphosphoryl]methyl]pentanedioate
• CAS: 174280-83-2
• 化学式: C₂₉H₄₁NO₁₁P₂
• 分子量: 641.592
• InChiKey: XPWNXSWGGJUIDB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  43
• 可旋转键数：
  22
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  153
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  2-({1-[6-(Diphenoxy-phosphoryloxy)-hexanoylamino]-ethyl}-methoxy-phosphinoylmethyl)-pentanedioic acid dimethyl ester 在 platinum(IV) oxide sodium hydroxide 、 三辛胺 、 AG 50W-X₈ 、 氢气 作用下， 反应 95.0h， 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：

  6-羟基己酸 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 吡啶 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 生成 2-({1-[6-(Diphenoxy-phosphoryloxy)-hexanoylamino]-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

• 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.