二甲基[溴(苯基)甲基]膦酸酯 | 92074-48-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 中文名称: 二甲基[溴(苯基)甲基]膦酸酯
• 英文名称: dimethyl α-bromobenzylphosphonate
• 英文别名: dimethyl [bromo(phenyl)methyl]phosphonate；[bromo(dimethoxyphosphoryl)methyl]benzene
• CAS: 92074-48-1
• 化学式: C₉H₁₂BrO₃P
• 分子量: 279.07
• InChiKey: SWULVVDIIDLOSX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  二甲基[溴(苯基)甲基]膦酸酯 在 三甲基溴硅烷 作用下， 以 二氯甲烷 为溶剂， 反应 20.0h， 以85%的产率得到α-Brombenzylphosphonsaeure
  参考文献：
  名称：

  [EN] METHODS AND SYSTEMS FOR PREPARING IRREVERSIBLE INHIBITORS OF PROTEIN TYROSINE PHOSPHATASES
  [FR] PROCÉDÉS ET SYSTÈMES POUR PRÉPARER DES INHIBITEURS IRRÉVERSIBLES DE PROTÉINES TYROSINES PHOSPHATASES

  摘要：

  在本发明中，描述了新颖的溴代磷酰甲基苯丙氨酸氨基酸衍生物（BrPmp）及其含BrPmp肽段的制备和应用，这些衍生物是特异性的、不可逆的蛋白酪氨酸磷酸酶抑制剂，适用于肽合成中的应用。这些衍生物的合成既简单又可放大，适合于肽合成。所述的BrPmp衍生物可以适当地进行保护，以便进行固相肽合成（SPPS）并并入肽中，用于制备蛋白酪氨酸磷酸酶抑制剂和抑制剂库。所得到的肽和肽库可用于识别新的蛋白酪氨酸磷酸酶特异序列，并在细胞裂解液、诊断样本和活检样本中分析蛋白酪氨酸磷酸酶的活性。

  公开号：

  WO2011106898A1
• 作为产物：
  描述：

  苯甲醛 在 吡啶 potassium fluoride 、 二溴亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 0.42h， 生成 二甲基[溴(苯基)甲基]膦酸酯
  参考文献：
  名称：

  [EN] METHODS AND SYSTEMS FOR PREPARING IRREVERSIBLE INHIBITORS OF PROTEIN TYROSINE PHOSPHATASES
  [FR] PROCÉDÉS ET SYSTÈMES POUR PRÉPARER DES INHIBITEURS IRRÉVERSIBLES DE PROTÉINES TYROSINES PHOSPHATASES

  摘要：

  在本发明中，描述了新颖的溴代磷酰甲基苯丙氨酸氨基酸衍生物（BrPmp）及其含BrPmp肽段的制备和应用，这些衍生物是特异性的、不可逆的蛋白酪氨酸磷酸酶抑制剂，适用于肽合成中的应用。这些衍生物的合成既简单又可放大，适合于肽合成。所述的BrPmp衍生物可以适当地进行保护，以便进行固相肽合成（SPPS）并并入肽中，用于制备蛋白酪氨酸磷酸酶抑制剂和抑制剂库。所得到的肽和肽库可用于识别新的蛋白酪氨酸磷酸酶特异序列，并在细胞裂解液、诊断样本和活检样本中分析蛋白酪氨酸磷酸酶的活性。

  公开号：

  WO2011106898A1

文献信息

• Palladium-Catalyzed Migratory Insertion of Isocyanides for Synthesis of <i>C</i>-Phosphonoketenimines
  作者：Qiang Yang、Chong Li、Ming-Xing Cheng、Shang-Dong Yang

  DOI：10.1021/acscatal.6b01253

  日期：2016.7.1

  An efficient method for the synthesis of C-phosphonoketenimines through palladium-catalyzed migratory insertion of isocyanides has been developed for the first time. This procedure tolerates wide functional groups and has a good atom economy. Further transformations of the products, which are useful building blocks for the β-aminophosphonates, β-aminovinylphosphonates, and C-phosphorylated tetrazoles

  首次开发了通过钯催化的异氰酸酯迁移插入合成C-膦烯酮的有效方法。该程序可耐受广泛的官能团，并具有良好的原子经济性。产物的进一步转化是潜在的合成用途，所述产物是β-氨基膦酸酯，β-氨基乙烯基膦酸酯和C-磷酸化的四唑的有用的结构单元。
• Methods and Systems for Preparing Irreversible Inhibitors of Protein Tyrosine Phosphatases
  申请人：Cairo Christopher Warren

  公开号：US20130165333A1

  公开（公告）日：2013-06-27

  Described herein are the preparation and use of novel bromo-phosphonomethylphenylalanine amino acid derivatives (BrPmp) and BrPmp-containing peptides as specific, irreversible protein tyrosine phosphatase inhibitors, which are suitable for application in peptide synthesis. These derivatives are particularly advantageous since their synthesis is both easy and scalable, and they are suitable for peptide synthesis. The BrPmp derivatives described herein can be appropriately protected to allow for solid phase peptide synthesis (SPPS) and incorporation into peptides for preparation of protein tyrosine phosphatase inhibitors and inhibitor libraries. The peptides and peptide libraries can be used to identify new protein tyrosine phosphatase specific sequences and profile protein tyrosine phosphatase activity in cell lysates, diagnostic samples and biopsy samples.

  本文描述了一种新型溴代磷酸甲基苯丙氨酸氨基酸衍生物（BrPmp）和含有BrPmp的肽的制备和使用，作为特异性、不可逆的蛋白酪氨酸磷酸酶抑制剂，适用于肽合成。这些衍生物特别优越，因为它们的合成既容易又可扩展，并且它们适用于肽合成。本文所述的BrPmp衍生物可以适当地保护，以允许固相肽合成（SPPS）和将其纳入肽中，以制备蛋白酪氨酸磷酸酶抑制剂和抑制剂库。这些肽和肽库可用于识别新的蛋白酪氨酸磷酸酶特异性序列，并在细胞裂解物、诊断样本和活检样本中分析蛋白酪氨酸磷酸酶活性。
• Methods and systems for preparing irreversible inhibitors of protein tyrosine phosphatases
  申请人：Cairo Christopher Warren

  公开号：US09399653B2

  公开（公告）日：2016-07-26

  Described herein are the preparation and use of novel bromo-phosphonomethylphenylalanine amino acid derivatives (BrPmp) and BrPmp-containing peptides as specific, irreversible protein tyrosine phosphatase inhibitors, which are suitable for application in peptide synthesis. These derivatives are particularly advantageous since their synthesis is both easy and scalable, and they are suitable for peptide synthesis. The BrPmp derivatives described herein can be appropriately protected to allow for solid phase peptide synthesis (SPPS) and incorporation into peptides for preparation of protein tyrosine phosphatase inhibitors and inhibitor libraries. The peptides and peptide libraries can be used to identify new protein tyrosine phosphatase specific sequences and profile protein tyrosine phosphatase activity in cell lysates, diagnostic samples and biopsy samples.

  本文描述了一种新型溴代磷酸甲基苯丙氨酸衍生物（BrPmp）及其含有的肽作为特异性、不可逆的蛋白酪氨酸磷酸酶抑制剂的制备和应用，适用于肽合成。这些衍生物特别有优势，因为它们的合成既容易又可扩展，并且适用于肽合成。本文所描述的BrPmp衍生物可以适当保护，以允许固相肽合成（SPPS）和纳入肽中，以制备蛋白酪氨酸磷酸酶抑制剂和抑制剂库。这些肽和肽库可用于鉴定新的蛋白酪氨酸磷酸酶特异性序列，并在细胞裂解物、诊断样本和活检样本中分析蛋白酪氨酸磷酸酶活性。
• Collins, David J.; Drygala, Peter F.; Swan, John M., Australian Journal of Chemistry, 1984, vol. 37, # 5, p. 1009 - 1021
  作者：Collins, David J.、Drygala, Peter F.、Swan, John M.

  DOI：——

  日期：——
• A protected l-bromophosphonomethylphenylalanine amino acid derivative (BrPmp) for synthesis of irreversible protein tyrosine phosphatase inhibitors
  作者：Naresh S. Tulsi、A. Michael Downey、Christopher W. Cairo

  DOI：10.1016/j.bmc.2010.09.040

  日期：2010.12

  Protein tyrosine phosphatases (PTPs) are important therapeutic targets for medicinal chemists and biochemists. General strategies for the development of inhibitors of these enzymes are needed. Several modular strategies which rely on phosphotyrosine mimics are known for PTP inhibitors. Previous strategies include phosphonomethylphenylalanine (Pmp) derivatives which act as competitive inhibitors. Pmp amino acid derivatives have been used to develop specific inhibitors by incorporation into sequences recognized by the PTP of interest. We report the synthesis of a new phosphonotyrosine analog, L-phosphonobromomethylphenylalanine (BrPmp), which acts as an inhibitor of PTPs. The BrPmp derivative was prepared as an Fmoc-protected amino acid which can be used in standard solid phase peptide synthesis (SPPS) methods. The synthesis of the protected amino acid derivative requires 11 steps from tyrosine with a 30% overall yield. Enzyme inhibition studies with the PTP CD45 demonstrate that BrPmp derivatives are irreversible inhibitors of the enzyme. A tripeptide which incorporated BrPmp had increased inhibitory potency against PTP relative to BrPmp alone, confirming that the incorporation of BrPmp into peptide sequences provides additional context to improve enzyme binding. (c) 2010 Elsevier Ltd. All rights reserved.