benzyl benzylphosphonic acid | 100715-74-0

• 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: benzyl benzylphosphonic acid
• 英文别名: Benzyl-phenylmethoxyphosphinic acid；benzyl(phenylmethoxy)phosphinic acid
• CAS: 100715-74-0
• 化学式: C₁₄H₁₅O₃P
• 分子量: 262.245
• InChiKey: GKHCUIZVMCRMAT-UHFFFAOYSA-N

物化性质

• 熔点：
  103 °C
• 沸点：
  428.1±48.0 °C(Predicted)
• 密度：
  1.243±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  benzyl benzylphosphonic acid 在 palladium on activated charcoal 草酰氯 、 氢气 、 potassium carbonate 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 4.0h， 生成 N-[hydroxy(benzyl)phosphinyl]-L-glutamic acid tripotassium salt
  参考文献：
  名称：

  Probing for a hydrophobic a binding register in prostate-specific membrane antigen with phenylalkylphosphonamidates

  摘要：

  To explore for the existence of an auxiliary hydrophobic binding register remote from the active site of PSMA a series of phenylalkylphosphonamidate derivatives of glutamic acid were synthesized and evaluated for their inhibitory potencies against PSMA. Both the phenyl- and benzylphosphonamidates (1a and 1b) exhibited only modest inhibitory potency against. The phenethyl analog 1c was intermediate in inhibitory potency while inhibitors possessing a longer alkyl tether from the phenyl ring, resulted in markedly improved K-i values. The greatest inhibitory potency was obtained for the inhibitors in which the phenyl ring was extended furthest from the central phosphorus (if, n = 5 and I g, n = 6). The slightly serrated pattern that emerged as the alkyl tether increased from three to six methylene units suggests that inhibitory potency is not simply correlated to increased hydrophobicity imparted by the phenylalkyl chain, but rather that one or more hydrophobic binding registers may exist remote from the substrate recognition architecture in the active site of PSMA. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.06.031
• 作为产物：
  描述：

  亚磷酸二苄酯 在 双(三甲基硅烷基)氨基钾 、 sodium iodide 作用下， 以 四氢呋喃 、 甲苯 、 丁酮 为溶剂， 反应 5.0h， 生成 benzyl benzylphosphonic acid
  参考文献：
  名称：

  Probing for a hydrophobic a binding register in prostate-specific membrane antigen with phenylalkylphosphonamidates

  摘要：

  To explore for the existence of an auxiliary hydrophobic binding register remote from the active site of PSMA a series of phenylalkylphosphonamidate derivatives of glutamic acid were synthesized and evaluated for their inhibitory potencies against PSMA. Both the phenyl- and benzylphosphonamidates (1a and 1b) exhibited only modest inhibitory potency against. The phenethyl analog 1c was intermediate in inhibitory potency while inhibitors possessing a longer alkyl tether from the phenyl ring, resulted in markedly improved K-i values. The greatest inhibitory potency was obtained for the inhibitors in which the phenyl ring was extended furthest from the central phosphorus (if, n = 5 and I g, n = 6). The slightly serrated pattern that emerged as the alkyl tether increased from three to six methylene units suggests that inhibitory potency is not simply correlated to increased hydrophobicity imparted by the phenylalkyl chain, but rather that one or more hydrophobic binding registers may exist remote from the substrate recognition architecture in the active site of PSMA. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.06.031

文献信息

• Synthesis of adenosine-5′-phosphates and 5′-alkylphosphonates via the Mitsunobu reaction
  作者：Mourad Saady、Luc Lebeau、Charles Mioskowski

  DOI：10.1016/0040-4039(95)00234-4

  日期：1995.3

  The Mitsunobu reaction can be successfully applied to achieve phosphorylation and phosphonylation of purine nucleosides. A series of different adenosine-5′-phosphate analogs was obtained with good to excellent yields.

  Mitsunobu反应可以成功地用于实现嘌呤核苷的磷酸化和膦酰化。获得了一系列不同的具有良好至优异产率的不同的腺苷-5'-磷酸类似物。
• Phosphonic acid analogs of GABA through reductive dealkylation of phosphonic diesters with lithium trialkylborohydrides
  作者：Sarwat Chowdhury、Niraj J. Muni、Nicholas P. Greenwood、David R. Pepperberg、Robert F. Standaert

  DOI：10.1016/j.bmcl.2007.04.026

  日期：2007.7

  Lithium trialkylborohydrides were found to effect rapid monodealkylation of phosphonic diesters, and this reaction was applied to the synthesis of alkylphosphonic acid 2-aminoethyl esters [H(2)N(CH(2))(2)OP(OH)R, 4], a little-explored class of analogs of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Compound 4a (R=Me) proved to be a potent antagonist at human rho1 GABA(C) receptors

  发现三烷基硼氢化锂可实现膦酸二酯的快速单脱烷基化，并将该反应应用于烷基膦酸2-氨基乙基酯[H（2）N（CH（2））（2）OP（OH）R，4]的合成，是一种抑制神经递质γ-氨基丁酸（GABA）的类似药物，但尚未探索。化合物4a（R = Me）被证明是人类rho1 GABA（C）受体（在非洲爪蟾卵母细胞中表达的）的有效拮抗剂，IC（50）为11.1 microM，但在alpha（1）beta（2）处无活性）γ（2）GABA（A）受体。
• Tailoring the Specificity and Reactivity of a Mechanism-Based Inactivator of Glucocerebrosidase for Potential Therapeutic Applications
  作者：Brian P. Rempel、Michael B. Tropak、Don J. Mahuran、Stephen G. Withers

  DOI：10.1002/anie.201103924

  日期：2011.10.24

  Chaperoning an enzyme: Fluorosugar glycosidase inactivators with tunable phosphorus‐based leaving groups react quickly with the catalytic nucleophile in β glucocerebrosidase (blue circle; Bn=benzyl). In Western blot analysis, Gaucher patient cells treated with these inactivators show increased intracellular levels of mutant enzyme, presumably because of increased transit from the endoplasmic reticulum

  陪伴酶：具有可调磷基离去基团的氟糖糖苷酶灭活剂与 β 葡糖脑苷脂酶中的催化亲核试剂快速反应（蓝色圆圈；Bn=苄基）。在蛋白质印迹分析中，用这些灭活剂处理的戈谢患者细胞显示出细胞内突变酶水平增加，可能是因为从内质网（淡蓝色）到溶酶体（淡粉色）的转运增加。
• Phosphodiesters serve as potentially tunable aglycones for fluoro sugar inactivators of retaining β-glycosidases
  作者：B. P. Rempel、S. G. Withers

  DOI：10.1039/c4ob00235k

  日期：——

  2-Deoxy-2-fluoroglycosides were synthesised and tested as covalent glycosidase inactivators. β-d-Gluco-, -manno- and -galacto-configured benzyl-benzylphosphonate derivatives efficiently inactivate β-gluco-, β-manno- and β-galactosidases, while α-gluco- and α-manno-configured phosphate and phosphonate derivatives instead served as slow substrates for their cognate α-glycosidases.

  2-脱氧-2-氟糖苷被合成并测试作为共价糖苷酶不活化剂。β-d-葡萄糖、-甘露糖和-半乳糖构型的苄基-苄基膦酸酯衍生物有效地不活化β-葡萄糖、β-甘露糖和β-半乳糖酶，而α-葡萄糖和α-甘露糖构型的磷酸盐和膦酸盐衍生物则作为其相应α-糖苷酶的缓慢底物。
• Fungal Glycolipid Hydrolase Inhibitors and Their Effect on<i>Cryptococcus neoformans</i>
  作者：Andres G. Santana、Christina Tysoe、Guanggan Hu、James Kronstad、Ethan D. Goddard-Borger、Stephen G. Withers

  DOI：10.1002/cbic.201600538

  日期：2017.2.1

  A library of iminosugar derivatives was tested against the fungal enzymes EGCrP‐1 and 2; this allowed the identification of nanomolar‐range inhibitors, such as 17. Several inhibitors were tested against C. neoformans and showed growth‐inhibitory activity towards the acapsular strain.

  测试了亚氨基糖衍生物库针对真菌酶EGCrP-1和2的作用；这样就可以鉴定出纳摩尔范围的抑制剂，例如17。测试了几种抑制剂对新孢梭菌的抑制作用，并显示了对荚膜菌株的生长抑制活性。