O,O-dicyclopropylmethylphosphoroamidate | 6698-23-3

• 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: O,O-dicyclopropylmethylphosphoroamidate
• 英文别名: Dicyclopropylcarbinyl-phosphoramid
• CAS: 6698-23-3
• 化学式: C₈H₁₆NO₃P
• 分子量: 205.194
• InChiKey: BSXWXBRKHUSXIJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.91
• 重原子数：
  13.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  61.55
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  Dicyclopropylcarbinyl-phosphorochloridat 在 氨 作用下， 以 四氯化碳 为溶剂， 生成 O,O-dicyclopropylmethylphosphoroamidate
  参考文献：
  名称：

  二环丙基碳酰氯磷酸酯的制备及其在磷酸化反应中的应用

  摘要：

  已经合成了用于磷酸化反应的二环丙基羰基磷酰氯。该试剂和伯或仲醇产生相应的酯。它与核苷的伯羟基和仲羟基官能团反应形成核苷酸三酯。用酸水溶液将磷酸二环丙基羰基甲基酯水解为磷酸单薄荷酯。核苷酸三酯产生的游离核苷酸的量反映了它们在酸中的不稳定性，因此，从2'，3'-异亚丙基-尿苷中产生的尿苷5'磷酸盐的总产率为53％，而在12中仅获得了胸苷3'的磷酸盐。 ％来自5′-O-三苯甲基胸苷。

  DOI：

  10.1016/0040-4020(66)80003-0

文献信息

• Binding of a Designed Substrate Analogue to Diisopropyl Fluorophosphatase:  Implications for the Phosphotriesterase Mechanism
  作者：Marc-Michael Blum、Frank Löhr、Andre Richardt、Heinz Rüterjans、Julian C.-H. Chen

  DOI：10.1021/ja061887n

  日期：2006.10.1

  A wide range of organophosphorus nerve agents, including Soman, Sarin, and Tabun is efficiently hydrolyzed by the phosphotriesterase enzyme diisopropyl fluorophosphatase (DFPase) from Loligo vulgaris. To date, the lack of available inhibitors of DFPase has limited studies on its mechanism. The de novo design, synthesis, and characterization of substrate analogues acting as competitive inhibitors of DFPase are reported. The 1.73 A crystal structure of O,O-dicyclopentylphosphoroamidate (DcPPA) bound to DFPase shows a direct coordination of the phosphoryl oxygen by the catalytic calcium ion. The binding mode of this substrate analogue suggests a crucial role for electrostatics in the orientation of the ligand in the active site. This interpretation is further supported by the crystal structures of double mutants D229N/N120D and D229N/N175D, designed to reorient the electrostatic environment around the catalytic calcium. The structures show no differences in their calcium coordinating environment, although they are enzymatically inactive. Additional double mutants E21Q/N120D and E21Q/N175D are also inactive. On the basis of these crystal structures and kinetic and mutagenesis data as well as isotope labeling we propose a new mechanism for DFPase activity. Calcium coordinating residue D229, in concert with direct substrate activation by the metal ion, renders the phosphorus atom of the substrate susceptible for attack of water, through generation of a phosphoenzyme intermediate. Our proposed mechanism may be applicable to the structurally related enzyme paraoxonase (PON), a component of high-density lipoprotein (HDL).