methyl bis(2-methoxycarbonylethyl)phosphinate | 57384-29-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl bis(2-methoxycarbonylethyl)phosphinate
• 英文别名: Dimethyl 3,3'-(methoxyphosphoryl)dipropanoate；methyl 3-[methoxy-(3-methoxy-3-oxopropyl)phosphoryl]propanoate
• CAS: 57384-29-9
• 化学式: C₉H₁₇O₆P
• 分子量: 252.204
• InChiKey: VYJSLEQQXVSPJQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  16
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  78.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl bis(2-methoxycarbonylethyl)phosphinate 在 盐酸 、 sodium tert-pentoxide 作用下， 以 水 、 苯 为溶剂， 反应 24.0h， 生成 1-hydroxy-1-oxophosphorinan-4-one
  参考文献：
  名称：

  Inhibition of glutamate racemase by substrate–product analogues

  摘要：

  D-Glutamate is an essential biosynthetic building block of the peptidoglycans that encapsulate the bacterial cell wall. Glutamate racemase catalyzes the reversible formation of D-glutamate from L-glutamate and, hence, the enzyme is a potential therapeutic target. We show that the novel cyclic substrate-product analogue (R,S)-1-hydroxy-1-oxo-4-amino-4-carboxyphosphorinane is a modest, partial noncompetitive inhibitor of glutamate racemase from Fusobacterium nucleatum (FnGR), a pathogen responsible, in part, for periodontal disease and colorectal cancer (K-i = 3.1 +/- 0.6 mM, cf. K-m = 1.41 +/- 0.06 mM). The cyclic substrate- product analogue (R, S)-4-amino-4-carboxy-1,1-dioxotetrahydro-thiopyran was a weak inhibitor, giving only similar to 30% inhibition at a concentration of 40 mM. The related cyclic substrate-product analogue 1,1-dioxo-tetrahydrothiopyran-4-one was a cooperative mixed-type inhibitor of FnGR (K-i = 18.4 +/- 1.2 mM), while linear analogues were only weak inhibitors of the enzyme. For glutamate racemase, mimicking the structure of both enantiomeric substrates (substrate-product analogues) serves as a useful design strategy for developing inhibitors. The new cyclic compounds developed in the present study may serve as potential lead compounds for further development. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.12.114
• 作为产物：
  描述：

  3-(methoxyphosphinyl)propanoic acid methyl ester 、 丙烯酸甲酯（MA） 在 sodium methylate 作用下， 以76%的产率得到methyl bis(2-methoxycarbonylethyl)phosphinate
  参考文献：
  名称：

  Inhibition of glutamate racemase by substrate–product analogues

  摘要：

  D-Glutamate is an essential biosynthetic building block of the peptidoglycans that encapsulate the bacterial cell wall. Glutamate racemase catalyzes the reversible formation of D-glutamate from L-glutamate and, hence, the enzyme is a potential therapeutic target. We show that the novel cyclic substrate-product analogue (R,S)-1-hydroxy-1-oxo-4-amino-4-carboxyphosphorinane is a modest, partial noncompetitive inhibitor of glutamate racemase from Fusobacterium nucleatum (FnGR), a pathogen responsible, in part, for periodontal disease and colorectal cancer (K-i = 3.1 +/- 0.6 mM, cf. K-m = 1.41 +/- 0.06 mM). The cyclic substrate- product analogue (R, S)-4-amino-4-carboxy-1,1-dioxotetrahydro-thiopyran was a weak inhibitor, giving only similar to 30% inhibition at a concentration of 40 mM. The related cyclic substrate-product analogue 1,1-dioxo-tetrahydrothiopyran-4-one was a cooperative mixed-type inhibitor of FnGR (K-i = 18.4 +/- 1.2 mM), while linear analogues were only weak inhibitors of the enzyme. For glutamate racemase, mimicking the structure of both enantiomeric substrates (substrate-product analogues) serves as a useful design strategy for developing inhibitors. The new cyclic compounds developed in the present study may serve as potential lead compounds for further development. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.12.114

文献信息

• 1-Oxo-2-oxa-1-phosphabicyclo[2.2.2]octane:  A New Mechanistic Probe for the Basic Hydrolysis of Phosphate Esters
  作者：Andrzej E. Wróblewski、John G. Verkade

  DOI：10.1021/ja9611147

  日期：1996.1.1

  title compound 2 was accomplished in a multistep sequence starting from hypophosphorous acid. In strong base, the bicyclic phosphinate 2 hydrolyzes 2 orders of magnitude faster than the bicyclic phosphate OP(OCH2)3CCH3 (1a) and the acceleration is entirely enthalpic. This rate enhancement is attributed to the greater ease with which 2 achieves the five-coordinate transition state. The molecular structure

  从次磷酸开始以多步顺序完成标题化合物2的合成。在强碱中，双环次膦酸盐 2 的水解速度比双环磷酸盐 OP(OCH2)3CCH3 (1a) 快 2 个数量级，并且加速完全是焓。这种速率提高归因于 2 更容易实现五坐标过渡态。与 1a 相比，通过 X 射线方法确定的 2 的分子结构显示在任一双环框架内都没有应变的迹象。观察到的加速度不支持立体电子效应对六元环磷酸酯水解的贡献。
• Thermodynamic study of lanthanide(<scp>iii</scp>) complexes with bifunctional monophosphinic acid analogues of H₄dota and comparative kinetic study of yttrium(<scp>iii</scp>) complexes
  作者：Michaela Försterová、Ivona Svobodová、Přemysl Lubal、Petr Táborský、Jan Kotek、Petr Hermann、Ivan Lukeš

  DOI：10.1039/b613404a

  日期：——

  of yttrium(III) complexes with a series of H(4)dota-like ligands (H(4)dota and its phosphinic/phosphonic acid analogues) were studied and the reactions are sensitive to a slight modification of the ligand structure. The (2-carboxyethyl)phosphinic acid derivative H(5)do3ap(PrA) and the phosphonic acid ligand H(5)do3ap form complexes faster than H(4)dota. The most kinetically inert complex is that with

  具有三个乙酸和一个次膦酸侧链和丙酸酯（H（5）do3ap（PrA））或4-氨基苄基（H（4）do3ap（ABn））反应性基团的新双功能H（4）dota状配体研究了磷原子。电位研究表明，配体与母体H（4）dota具有相似的碱性，并且它们与钠（i）和选定的镧系元素（III）离子形成的配合物的稳定性常数也相似。与一系列H（4）dota状配体（H（4）dota及其次膦酸/膦酸类似物）的钇（III）配合物的形成和酸辅助解聚动力学进行了研究，反应对轻微的修饰敏感配体结构。（2-羧乙基）次膦酸衍生物H（5）do3ap（PrA）和膦酸配体H（5）do3ap形成络合物比H（4）dota更快。最具有动力学惰性的复合物是H（4）do3ap（ABn）。络合和解络的速率可取决于质子在复合腔内外转移的能力，因此取决于配体的疏水性。结果表明，新的双功能配体适合用于钇（iii）放射性同位素标记生物分子，用于核医学。
• Inhibition of glutamate racemase by substrate–product analogues
  作者：Mohan Pal、Stephen L. Bearne

  DOI：10.1016/j.bmcl.2013.12.114

  日期：2014.3

  D-Glutamate is an essential biosynthetic building block of the peptidoglycans that encapsulate the bacterial cell wall. Glutamate racemase catalyzes the reversible formation of D-glutamate from L-glutamate and, hence, the enzyme is a potential therapeutic target. We show that the novel cyclic substrate-product analogue (R,S)-1-hydroxy-1-oxo-4-amino-4-carboxyphosphorinane is a modest, partial noncompetitive inhibitor of glutamate racemase from Fusobacterium nucleatum (FnGR), a pathogen responsible, in part, for periodontal disease and colorectal cancer (K-i = 3.1 +/- 0.6 mM, cf. K-m = 1.41 +/- 0.06 mM). The cyclic substrate- product analogue (R, S)-4-amino-4-carboxy-1,1-dioxotetrahydro-thiopyran was a weak inhibitor, giving only similar to 30% inhibition at a concentration of 40 mM. The related cyclic substrate-product analogue 1,1-dioxo-tetrahydrothiopyran-4-one was a cooperative mixed-type inhibitor of FnGR (K-i = 18.4 +/- 1.2 mM), while linear analogues were only weak inhibitors of the enzyme. For glutamate racemase, mimicking the structure of both enantiomeric substrates (substrate-product analogues) serves as a useful design strategy for developing inhibitors. The new cyclic compounds developed in the present study may serve as potential lead compounds for further development. (C) 2013 Elsevier Ltd. All rights reserved.