ethyl aminomethyl<(diethoxyphosphoryl)methyl>phosphinate | 240432-54-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物
• 英文名称: ethyl aminomethyl<(diethoxyphosphoryl)methyl>phosphinate
• CAS: 240432-54-6
• 化学式: C₈H₂₁NO₅P₂
• 分子量: 273.206
• InChiKey: OSMRZBKJXMEVRV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.44
• 重原子数：
  16.0
• 可旋转键数：
  9.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  87.85
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  ethyl aminomethyl<(diethoxyphosphoryl)methyl>phosphinate 在 sodium hydroxide 、 三甲基溴硅烷 作用下， 生成 sodium aminomethyl (dihydroxyphosphorylmethyl)phosphinate
  参考文献：
  名称：

  α-Functionalized Phosphonylphosphinates:  Synthesis and Evaluation as Transcarbamoylase Inhibitors

  摘要：

  Diverse alpha-methyl-substituted phosphonylphosphinates (P-C-P-C-X) are accessible from a protected, pentafluorophenylsulfonated phosphonylphosphinate via nucleophilic displacement. The utility of this route is demonstrated with several nitrogen nucleophiles. The resulting amine and amino acid phosphonylphosphinate derivatives were evaluated as inhibitors of Streptococcus faecalis ornithine transcarbamoylase (OTC). Compared with the structurally related phosphonoacetyl-L-ornithine (L-PALO), a known inhibitor of OTCs from various sources, the phosphonylphosphinates are surprisingly poor inhibitors, binding several orders of magnitude less tightly to the enzyme. These results suggest that the tetrahedral intermediate formed in the normal transcarbamoylase reaction is poorly mimicked by a tetrahedral and anionic phosphonate, either because of directly unfavorable interactions with a hydrogen-bond acceptor within the active site or because transition-state analogues are unable to induce the protein conformation changes that normally accompany reaction.

  DOI：

  10.1021/jm991008q
• 作为产物：
  描述：

  <(diethoxyphosphoryl)methyl(ethoxy)phosphoryl>methyl 2,3,4,5,6-pentafluorobenzenesulfonate 在 palladium on activated charcoal sodium azide 、 氢气 作用下， 以 乙醇 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 41.0h， 生成 ethyl aminomethyl<(diethoxyphosphoryl)methyl>phosphinate
  参考文献：
  名称：

  α-Functionalized Phosphonylphosphinates:  Synthesis and Evaluation as Transcarbamoylase Inhibitors

  摘要：

  Diverse alpha-methyl-substituted phosphonylphosphinates (P-C-P-C-X) are accessible from a protected, pentafluorophenylsulfonated phosphonylphosphinate via nucleophilic displacement. The utility of this route is demonstrated with several nitrogen nucleophiles. The resulting amine and amino acid phosphonylphosphinate derivatives were evaluated as inhibitors of Streptococcus faecalis ornithine transcarbamoylase (OTC). Compared with the structurally related phosphonoacetyl-L-ornithine (L-PALO), a known inhibitor of OTCs from various sources, the phosphonylphosphinates are surprisingly poor inhibitors, binding several orders of magnitude less tightly to the enzyme. These results suggest that the tetrahedral intermediate formed in the normal transcarbamoylase reaction is poorly mimicked by a tetrahedral and anionic phosphonate, either because of directly unfavorable interactions with a hydrogen-bond acceptor within the active site or because transition-state analogues are unable to induce the protein conformation changes that normally accompany reaction.

  DOI：

  10.1021/jm991008q

文献信息

• A guanidinium-based inhibitor of a type I isopentenyl diphosphate isomerase
  作者：Walid M. Abdelmagid、Niusha Mahmoodi、Martin E. Tanner

  DOI：10.1016/j.bmcl.2020.127577

  日期：2020.11

  inhibitor bound with high micromolar affinity and did not bind more tightly than an isosteric inhibitor lacking the guanidinium functionality. When tested against the Type I isopentenyl diphosphate:dimethylallyl diphosphate isomerase from Escherichia coli, the inhibitor bound with a Ki value of 120 nM, which was 400 times greater than its isosteric counterpart. This strategy of inhibition was much more

  设计一种带有附加到胍基官能团上的膦基膦酸酯基的抑制剂，以抑制从二甲基烯丙基二磷酸产生碳正离子的酶。当针对人类法呢基二磷酸合酶进行测试时，该抑制剂以高微摩尔亲和力结合，并且与缺乏胍基官能团的等排抑制剂相比，结合不紧密。当针对来自大肠杆菌的I型异戊烯基二磷酸异戊烯基：二甲基烯丙基二磷酸异构酶进行测试时，该抑制剂与K i结合120 nM的值，是其等排对应物的400倍。这种抑制策略对于产生碳阳离子的酶更为有效，该碳阳离子不能通过共振和离子对稳定，这可能是因为酶上有更多的进化压力来稳定阳离子。
• Studies with Guanidinium- and Amidinium-Based Inhibitors Suggest Minimal Stabilization of Allylic Carbocation Intermediates by Dehydrosqualene and Squalene Synthases
  作者：Walid M. Abdelmagid、Taniya Adak、Jon O. Freeman、Martin E. Tanner

  DOI：10.1021/acs.biochem.8b00731

  日期：2018.9.25

  An inhibitor bearing a neutral urea moiety was also prepared as a control. The positively charged inhibitors acted as competitive inhibitors against Staphylococcus aureus dehydrosqualene synthase with Ki values in the low micromolar range. Surprisingly, the neutral urea inhibitor was the most potent of the three. Similar trends were seen with the first half reaction of human squalene synthase. One

  脱氢角鲨烯和角鲨烯合酶分别催化氧化法中性和法呢基二磷酸的还原，头对头二聚化。在每种情况下，认为反应是通过法呢基二磷酸的初始离解而进行的，以形成烯丙基碳正离子-焦磷酸根离子对。这项工作描述了抑制剂的合成和测试，其中胍基或am基部分侧接有膦酰基次膦酸酯基和烃尾。这些官能团带有平面的，离域的正电荷，因此应作为烯丙基碳正离子的出色模拟物。还制备了带有中性脲部分的抑制剂作为对照。带正电荷的抑制剂可作为抗金黄色葡萄球菌脱氢角鲨烯合酶的竞争性抑制剂。ķ我值在低微摩尔范围内。令人惊讶的是，中性尿素抑制剂是这三种中最有效的。人角鲨烯合酶的上半年反应也看到了类似的趋势。这些结果的一种解释是这些酶的活性位点不会通过静电或π-阳离子相互作用直接稳定烯丙基碳正离子化。取而代之的是，这些酶可能与焦磷酸盐和脂质部分紧密结合，以促进催化作用，并且所结合的焦磷酸盐产物可提供碳阳离子的静电稳定作用。另一种可能性是这些抑制剂不