(S)-α-<<(1,1-dimethylethoxy)carbonyl>amino>-4-<2-(methyloxy)-2-oxoethyl>benzenepropanoic acid | 123993-31-7

• 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: (S)-α-<<(1,1-dimethylethoxy)carbonyl>amino>-4-<2-(methyloxy)-2-oxoethyl>benzenepropanoic acid
• 英文别名: (N-tert-butyloxycarbonyl)-4-(carbomethoxymethyl)-L-phenylalanine；(S)-2-((tert-Butoxycarbonyl)amino)-3-(4-(2-methoxy-2-oxoethyl)phenyl)propanoic acid；(2S)-3-[4-(2-methoxy-2-oxoethyl)phenyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid
• CAS: 123993-31-7
• 化学式: C₁₇H₂₃NO₆
• 分子量: 337.373
• InChiKey: SQUFBRDZJVBXNH-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-α-<<(1,1-dimethylethoxy)carbonyl>amino>-4-<2-(methyloxy)-2-oxoethyl>benzenepropanoic acid 在 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.33h， 生成 3-[2'-(S)-amino-3-(4''-methoxycarbonylmethyl)benzene]propanoylamino-1-(4-methoxybenzyl)-4-methyl-2-pyridone
  参考文献：
  名称：

  Nonpeptidic, Monocharged, Cell Permeable Ligands for the p56lck SH2 Domain

  摘要：

  p561ck is a member of the src family of tyrosine kinases and plays a critical role in the signal transduction events that lead to T cell activation. Ligands for the p561ck SH2 domain have the potential to disrupt the interaction of p561ck with its substrates and derail the signaling cascade that leads to the production of cytokines such as interleukin-2. Starting from the quintuply charged (at physiological pH) phosphorylated tetrapeptide, AcpYEEI, we recently disclosed (J. Med. Chem. 1999, 42, 722 and J. Med. Chem. 1999, 42, 1757) the design of the modified dipeptide 3, which carries just two charges at physiological pH. Here we present the elaboration of 3 to the nonpeptidic, monocharged compound, 9S. This molecule displays good binding affinity for the p561ck SH2 domain (K-d 1 muM) and good cell permeation, and this combination of properties allowed us to demonstrate clear-cut inhibitory effects on a very early event in T cell activation, namely calcium mobilization.

  DOI：

  10.1021/jm000446q
• 作为产物：
  描述：

  (S)-α-<<(1,1-dimethylethoxy)carbonyl>amino>-4-<2-(methyloxy)-2-oxoethyl>benzenepropanoic acid phenylmethylester 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 (S)-α-<<(1,1-dimethylethoxy)carbonyl>amino>-4-<2-(methyloxy)-2-oxoethyl>benzenepropanoic acid
  参考文献：
  名称：

  Preparation of carboalkoxyalkylphenylalanine derivatives from tyrosine

  摘要：

  DOI：

  10.1021/jo00290a021

文献信息

• Improved synthesis of [p-phosphono and p-sulfo]methylphenylalanine. Resolution of [p-phosphono-, p-sulfo-, p-car☐y-and p-N-hydroxycar☐amido-]methylphenylalanine.
  作者：Christiane Garbay-Jaureguiberry、Isabelle McCort-Tranchepain、Brigitte Barbe、Damien Ficheux、Bernard P. Roques

  DOI：10.1016/s0957-4166(00)82297-1

  日期：1992.5

  proteins, we recently synthesized the new amino acids, p(CH2PO3H2)Phe and p(CH2SO3H)Phe (D,L mixtures) as chemically and enzymatically stable analogs of (O-phospho) and (O-sulfo)-tyrosine. Here, we report improved syntheses of these amino acids and of their N-Boc protected derivatives for use in solid-phase peptide synthesis. A protocol for their enzymatic resolution by use of subtilisin Carlsberg esterase

  为了分析酪氨酸在肽和蛋白质中的翻译后磷酸化和硫酸化的作用，我们最近合成了新的氨基酸p（CH 2 PO 3 H 2）Phe和p（CH 2 SO 3 H）Phe（D，L混合物）作为（O-磷酸）和（O-磺基）酪氨酸的化学和酶促稳定类似物。在这里，我们报告了这些氨基酸及其N-Boc保护的衍生物用于固相肽合成的合成方法的改进。开发了一种使用枯草杆菌蛋白酶嘉士伯酯酶进行酶解的方案，并将其扩展到修饰氨基酸p（CH 2 CO 2 H）-D，L-Phe和p（CH 2CONHOH）-D，L-Phe。通过手性相HPLC测试拆分的氨基酸的光学纯度。给出了这些氨基酸及其N-Boc衍生形式的物理常数，包括其在PTC形式下的表征（苯硫代氨基甲酰基）。
• TILLEY, JEFFERSON W.;SARABU, RAMAKANTH;WAGNER, ROLF;MULKERINS, KATHLEEN, J. ORG. CHEM., 55,(1990) N, C. 906-910
  作者：TILLEY, JEFFERSON W.、SARABU, RAMAKANTH、WAGNER, ROLF、MULKERINS, KATHLEEN

  DOI：——

  日期：——
• Preparation of carboalkoxyalkylphenylalanine derivatives from tyrosine
  作者：Jefferson W. Tilley、Ramakanth Sarabu、Rolf Wagner、Kathleen Mulkerins

  DOI：10.1021/jo00290a021

  日期：1990.2
• Nonpeptidic, Monocharged, Cell Permeable Ligands for the p56lck SH2 Domain
  作者：John R. Proudfoot、Rajashehar Betageri、Mario Cardozo、Thomas A. Gilmore、Susan Glynn、Eugene R. Hickey、Scott Jakes、Alisa Kabcenell、Thomas M. Kirrane、Annette K. Tibolla、Susan Lukas、Usha R. Patel、Rajiv Sharma、Mehran Yazdanian、Neil Moss、Pierre L. Beaulieu、Dale R. Cameron、Jean-Marie Ferland、Jean Gauthier、James Gillard、Vida Gorys、Martin Poirier、Jean Rancourt、Dominik Wernic、Montse Llinas-Brunet

  DOI：10.1021/jm000446q

  日期：2001.7.1

  p561ck is a member of the src family of tyrosine kinases and plays a critical role in the signal transduction events that lead to T cell activation. Ligands for the p561ck SH2 domain have the potential to disrupt the interaction of p561ck with its substrates and derail the signaling cascade that leads to the production of cytokines such as interleukin-2. Starting from the quintuply charged (at physiological pH) phosphorylated tetrapeptide, AcpYEEI, we recently disclosed (J. Med. Chem. 1999, 42, 722 and J. Med. Chem. 1999, 42, 1757) the design of the modified dipeptide 3, which carries just two charges at physiological pH. Here we present the elaboration of 3 to the nonpeptidic, monocharged compound, 9S. This molecule displays good binding affinity for the p561ck SH2 domain (K-d 1 muM) and good cell permeation, and this combination of properties allowed us to demonstrate clear-cut inhibitory effects on a very early event in T cell activation, namely calcium mobilization.