2-(2-(3-hydroxyphenylamino)-2-oxoethylthio)acetic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(2-(3-hydroxyphenylamino)-2-oxoethylthio)acetic acid
• 英文别名: 2-[2-(3-Hydroxyanilino)-2-oxoethyl]sulfanylacetic acid
• 化学式: C₁₀H₁₁NO₄S
• mdl: MFCD02594717
• 分子量: 241.268
• InChiKey: GDPHDZMYEUGABH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  112
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(2-(3-hydroxyphenylamino)-2-oxoethylthio)acetic acid 在 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.0h， 生成 (R)-2,4-dihydroxy-N-(3-(2-(2-(2-(3-hydroxyphenylamino)-2-oxoethylthio)acetamido)ethylamino)-3-oxopropyl)-3,3-dimethylbutanamide
  参考文献：
  名称：

  Modeling Linear and Cyclic PKS Intermediates through Atom Replacement

  摘要：

  The mechanistic details of many polyketide synthases (PKSs) remain elusive due to the instability of transient intermediates that are not accessible via conventional methods. Here we report an atom replacement strategy that enables the rapid preparation of polyketone surrogates by selective atom replacement, thereby providing key substrate mimetics for detailed mechanistic evaluations. Polyketone mimetics are positioned on the actinorhodin acyl carrier protein (actACP) to probe the underpinnings of substrate association upon nascent chain elongation and processivity. Protein NMR is used to visualize substrate interaction with the actACP, where a tetraketide substrate is shown not to bind within the protein, while heptaketide and octaketide substrates show strong association between helix II and IV. To examine the later cyclization stages, we extended this strategy to prepare stabilized cyclic intermediates and evaluate their binding by the actACP. Elongated monocyclic mimics show much longer residence time within actACP than shortened analogs. Taken together, these observations suggest ACP-substrate association occurs both before and after ketoreductase action upon the fully elongated polyketone, indicating a key role played by the ACP within PKS timing and processivity. These atom replacement mimetics offer new tools to study protein and substrate interactions and are applicable to a wide variety of PKSs.

  DOI：

  10.1021/ja5064857
• 作为产物：
  描述：

  硫代羟基乙酸酐 、 3-氨基苯酚 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以97%的产率得到2-(2-(3-hydroxyphenylamino)-2-oxoethylthio)acetic acid
  参考文献：
  名称：

  Modeling Linear and Cyclic PKS Intermediates through Atom Replacement

  摘要：

  The mechanistic details of many polyketide synthases (PKSs) remain elusive due to the instability of transient intermediates that are not accessible via conventional methods. Here we report an atom replacement strategy that enables the rapid preparation of polyketone surrogates by selective atom replacement, thereby providing key substrate mimetics for detailed mechanistic evaluations. Polyketone mimetics are positioned on the actinorhodin acyl carrier protein (actACP) to probe the underpinnings of substrate association upon nascent chain elongation and processivity. Protein NMR is used to visualize substrate interaction with the actACP, where a tetraketide substrate is shown not to bind within the protein, while heptaketide and octaketide substrates show strong association between helix II and IV. To examine the later cyclization stages, we extended this strategy to prepare stabilized cyclic intermediates and evaluate their binding by the actACP. Elongated monocyclic mimics show much longer residence time within actACP than shortened analogs. Taken together, these observations suggest ACP-substrate association occurs both before and after ketoreductase action upon the fully elongated polyketone, indicating a key role played by the ACP within PKS timing and processivity. These atom replacement mimetics offer new tools to study protein and substrate interactions and are applicable to a wide variety of PKSs.

  DOI：

  10.1021/ja5064857