(1-(N-(tert-butyloxycarbonyl)amino)-3-phenylpropyl) phosphinic acid | 260390-87-2

• 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: (1-(N-(tert-butyloxycarbonyl)amino)-3-phenylpropyl) phosphinic acid
• 英文别名: (1-((tert-butoxycarbonyl)amino)-3-phenylpropyl)phosphinic acid
• CAS: 260390-87-2
• 化学式: C₁₄H₂₂NO₄P
• 分子量: 299.307
• InChiKey: XHFXPSXHKUGAAU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.94
• 重原子数：
  20.0
• 可旋转键数：
  5.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  75.63
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (1-(N-(tert-butyloxycarbonyl)amino)-3-phenylpropyl) phosphinic acid 在 sodium periodate 、 ruthenium(III) trichloride hydrate 、 三甲基硅烷化重氮甲烷 作用下， 以 乙醚 、 水 、 乙酸乙酯 、 甲苯 为溶剂， 反应 8.34h， 生成 Dimethyl 2-[[methoxy-[4-methoxy-1-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxobutyl]phosphoryl]methyl]pentanedioate
  参考文献：
  名称：

  Phosphinic acid-based inhibitors of tubulin polyglutamylases

  摘要：

  Tubulin is subject to a reversible post-translational modification involving polyglutamylation and deglutamylation of glutamate residues in its C-terminal tail. This process plays key roles in regulating the function of microtubule associated proteins, neuronal development, and metastatic progression. This study describes the synthesis and testing of three phosphinic acid-based inhibitors that have been designed to inhibit both the glutamylating and deglutamylating enzymes. The compounds were tested against the polyglutamylase TTLL7 using tail peptides as substrates (100 mu M) and the most potent inhibitor displayed an IC50 value of 150 mu M. The incorporation of these compounds into tubulin C-terminal tail peptides may lead to more potent TTLL inhibitors. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.05.069
• 作为产物：
  描述：

  二碳酸二叔丁酯 、 (R,S)-((1-amino)-3-phenylpropyl) phosphinic acid 在 三乙胺 作用下， 以 甲醇 为溶剂， 生成 (1-(N-(tert-butyloxycarbonyl)amino)-3-phenylpropyl) phosphinic acid
  参考文献：
  名称：

  A convenient method to synthesize phosphinic peptides containing an aspartyl or glutamyl aminophosphinic acid. Use of the phenyl group as the carboxyl synthon

  摘要：

  Many attempts to synthesize Asp Psi(PO2CH2)Ala phosphinic pseudodipeptides by Michael addition of aspartyl aminophosphinic acid to ethyl methacrylate have failed. The preparation of such phosphinic peptides was finally achieved starting from a protected Phe Psi(PO2CH2)Ala phosphinic building block. The key step is a mild oxidation of the phenyl group to carboxylic acid by use of the ruthenium trichloride-sodium metaperiodate system. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(99)00910-2

文献信息

• A synthetic method for diversification of the P1′ substituent in phosphinic dipeptides as a tool for exploration of the specificity of the S1′ binding pockets of leucine aminopeptidases
  作者：Stamatia Vassiliou、Metaxia Xeilari、Athanasios Yiotakis、Jolanta Grembecka、Małgorzata Pawełczak、Paweł Kafarski、Artur Mucha

  DOI：10.1016/j.bmc.2007.02.042

  日期：2007.5

  proteolytic enzymes, was elaborated. The procedure was based on parallel derivatization of the amino group in the suitably protected phosphinate building blocks with appropriate alkyl and aryl halides. This synthetic strategy represents an original approach to phosphinic dipeptide chemistry. Its usefulness was confirmed by obtaining a series of P1' modified phosphinic dipeptides, inhibitors of cytosolic leucine

  阐述了一种新的，通用的和通用的使次膦酸盐假二肽中的P1'位置多样化的方法，次膦酸盐假二肽可能是蛋白水解酶的抑制剂。该程序基于适当保护的次膦酸酯结构单元中的氨基与适当的烷基和芳基卤化物平行衍生而来。这种合成策略代表了次膦酸二肽化学的原始方法。通过基于结合在酶活性中的高苯丙氨酰基-苯丙氨酸类似物（hPheP [CH（2）] Phe）的结构的计算机辅助设计，获得了一系列P1'修饰的次膦酸二肽（胞质亮氨酸氨基肽酶的抑制剂），证实了其有用性。网站作为主导结构。在这种方法中，抑制剂P1'片段与酶的S1'区之间存在新颖的相互作用，尤其是涉及Asn330和Asp332酶残基的氢键被预测。讨论了对胞质亮氨酸氨基肽酶和氨基肽酶N的设计，合成和活性评估的细节。尽管先导化合物的效力没有提高，但是观察到合成抑制剂对两种研究的酶的显着选择性。