双[(4-联苯基)甲基]苯甲酰基膦酸酯 | 1059608-80-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 双[(4-联苯基)甲基]苯甲酰基膦酸酯
• 英文名称: bis[(4-biphenyl)methyl] phenacylphosphonate
• CAS: 1059608-80-8
• 化学式: C₃₄H₂₉O₄P
• 分子量: 532.576
• InChiKey: QDELFOLXAMGXNN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.83
• 重原子数：
  39.0
• 可旋转键数：
  11.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  52.6
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  双[(4-联苯基)甲基]苯甲酰基膦酸酯 在 sodium iodide 作用下， 以 丁酮 为溶剂， 反应 2.5h， 以77%的产率得到sodium biphenylmethyl 2-oxo-2-phenylethylphosphonate
  参考文献：
  名称：

  β-Ketophosphonates as β-lactamase inhibitors: Intramolecular cooperativity between the hydrophobic subsites of a class D β-lactamase

  摘要：

  A series of aryl and arylmethyl beta-aryl-beta-ketophosphonates have been prepared as potential beta-lactamase inhibitors. These compounds, as fast, reversible, competitive inhibitors, were most effective ( micromolar K(i) values) against the class D OXA-1 b-lactamase but had less activity against the OXA-10 enzyme. They were also quite effective against the class C b-lactamase of Enterobacter cloacae P99 but less so against the class A TEM-2 enzyme. Reduction of the keto group to form the corresponding beta-hydroxyphosphonates led to reduced inhibitory activity. Molecular modeling, based on the OXA-1 crystal structure, suggested interaction of the aryl groups with the hydrophobic elements of the enzyme's active site and polar interaction of the keto and phosphonate groups with the active site residues Ser 115, Lys 212 and Thr 213 and with the non-conserved Ser 258. Analysis of binding free energies showed that the beta-aryl and phosphonate ester aryl groups interacted cooperatively within the OXA-1 active site. Overall, the results suggest that quite effective inhibitors of class C and some class D beta-lactamases could be designed, based on the beta-ketophosphonate platform. (c) 2008 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2008.05.045
• 作为产物：
  描述：

  联苯-4-甲醇 、 diphenyl (2-oxo-2-phenylethyl)phosphonate 在 sodium hydride 作用下， 以 二甲基亚砜 、 甲苯 为溶剂， 反应 4.0h， 以57%的产率得到双[(4-联苯基)甲基]苯甲酰基膦酸酯
  参考文献：
  名称：

  β-Ketophosphonates as β-lactamase inhibitors: Intramolecular cooperativity between the hydrophobic subsites of a class D β-lactamase

  摘要：

  A series of aryl and arylmethyl beta-aryl-beta-ketophosphonates have been prepared as potential beta-lactamase inhibitors. These compounds, as fast, reversible, competitive inhibitors, were most effective ( micromolar K(i) values) against the class D OXA-1 b-lactamase but had less activity against the OXA-10 enzyme. They were also quite effective against the class C b-lactamase of Enterobacter cloacae P99 but less so against the class A TEM-2 enzyme. Reduction of the keto group to form the corresponding beta-hydroxyphosphonates led to reduced inhibitory activity. Molecular modeling, based on the OXA-1 crystal structure, suggested interaction of the aryl groups with the hydrophobic elements of the enzyme's active site and polar interaction of the keto and phosphonate groups with the active site residues Ser 115, Lys 212 and Thr 213 and with the non-conserved Ser 258. Analysis of binding free energies showed that the beta-aryl and phosphonate ester aryl groups interacted cooperatively within the OXA-1 active site. Overall, the results suggest that quite effective inhibitors of class C and some class D beta-lactamases could be designed, based on the beta-ketophosphonate platform. (c) 2008 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2008.05.045