tert-butyl 1-(2-chloroethylamino)-1-oxo-3-phenylpropan-2-ylcarbamate | 1579223-88-3

• 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: tert-butyl 1-(2-chloroethylamino)-1-oxo-3-phenylpropan-2-ylcarbamate
• 英文别名: tert-butyl N-[(2S)-1-(2-chloroethylamino)-1-oxo-3-phenylpropan-2-yl]carbamate
• CAS: 1579223-88-3
• 化学式: C₁₆H₂₃ClN₂O₃
• 分子量: 326.823
• InChiKey: NQWKWBMELOCLQL-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 1-(2-chloroethylamino)-1-oxo-3-phenylpropan-2-ylcarbamate 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 6.0h， 以81%的产率得到2-(N-Boc-1-amino-2-phenethyl)-2-oxazoline
  参考文献：
  名称：

  具有侧链l-脯氨酰胺部分的新型聚（2-恶唑啉），可作为直接不对称羟醛反应的有效有机催化剂†

  摘要：

  聚（2-恶唑啉）负载的双功能有机催化剂已通过自下而上的方法制备，该方法涉及合成明确定义的侧链中带有氨基的聚（2-恶唑啉）前体，然后将酰胺与N -Boc偶联。-大号脯氨酸然后去保护。结果L已经证明，在纯净条件下，环戊酰胺基官能化的聚合物比其单体对应物具有明显更高的活性，可以在几种条件下用几种取代的苯甲醛将环酮醛醇缩合。通过使用15mol％的聚合物作为催化剂，直接的羟醛反应产物以高收率和良好的非对映和对映选择性被分离。基于圆二色性光谱分析，催化活性的增强可能与聚（2-恶唑啉）s的假肽支架的构象变化有关。另外，这些可溶性聚合物催化剂可通过在乙醚中沉淀五个催化循环而回收和再利用，而不会显着降低其效率。

  DOI：

  10.1039/c6cy00448b
• 作为产物：
  描述：

  BOC-L-苯丙氨酸 在 四氯化碳 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三苯基膦 作用下， 以 二氯甲烷 为溶剂， 反应 5.5h， 生成 tert-butyl 1-(2-chloroethylamino)-1-oxo-3-phenylpropan-2-ylcarbamate
  参考文献：
  名称：

  Phenylalanine-Based Inactivator of AKT Kinase: Design, Synthesis, and Biological Evaluation

  摘要：

  Strategies to inhibit kinases by targeting the substrate binding site offer many advantages, including naturally evolved selectivity filters, but normally suffer from poor potency. In this work we propose a strategy to design and prepare covalent substrate-competitive kinase inhibitors as a method to improve potency. We have chosen Ala as the model kinase for this work. Using the AKT-GSK3 beta cocrystal structure and a reactive cysteine near the substrate binding site, we have identified phenylalanine (Phe) as an appropriate scaffold for the covalent inactivator portion of these inhibitors. By synthesizing compounds that incorporate cysteine-reactive electrophiles into phenylalanine and testing these compounds as AKT inhibitors, we have identified Boc-Phe-vinyl ketone as a submicromolar inactivator of AKT. We also show that Boc-Phe-vinyl ketone (1) potently inhibits AKT1 and inhibits cell growth in HCT116 and H460 cells nearly as well as AKT inhibitors GSK690693 and MK-2206, (2) is selective for kinases that possess an activation loop cysteine such as AKT, (3) requires the vinyl ketone for inactivation, (4) has inactivation that is time-dependent, and (5) alkylates Cys310 of AKT as shown by mass spectrometry. Identification of Boc-Phe-vinyl ketone as a covalent inactivator of AKT will allow the development of peptide and small-molecule substrate-competitive covalent kinase inhibitors that incorporate additional substrate binding elements to increase selectivity and potency. This proof-of-principle study also provides a basis to apply this strategy to other kinases of the AGC and CAMK families.

  DOI：

  10.1021/ml500088x

文献信息

• Phenylalanine-Based Inactivator of AKT Kinase: Design, Synthesis, and Biological Evaluation
  作者：Thuy Nguyen、Robert A. Coover、Jenson Verghese、Richard G. Moran、Keith C. Ellis

  DOI：10.1021/ml500088x

  日期：2014.5.8

  Strategies to inhibit kinases by targeting the substrate binding site offer many advantages, including naturally evolved selectivity filters, but normally suffer from poor potency. In this work we propose a strategy to design and prepare covalent substrate-competitive kinase inhibitors as a method to improve potency. We have chosen Ala as the model kinase for this work. Using the AKT-GSK3 beta cocrystal structure and a reactive cysteine near the substrate binding site, we have identified phenylalanine (Phe) as an appropriate scaffold for the covalent inactivator portion of these inhibitors. By synthesizing compounds that incorporate cysteine-reactive electrophiles into phenylalanine and testing these compounds as AKT inhibitors, we have identified Boc-Phe-vinyl ketone as a submicromolar inactivator of AKT. We also show that Boc-Phe-vinyl ketone (1) potently inhibits AKT1 and inhibits cell growth in HCT116 and H460 cells nearly as well as AKT inhibitors GSK690693 and MK-2206, (2) is selective for kinases that possess an activation loop cysteine such as AKT, (3) requires the vinyl ketone for inactivation, (4) has inactivation that is time-dependent, and (5) alkylates Cys310 of AKT as shown by mass spectrometry. Identification of Boc-Phe-vinyl ketone as a covalent inactivator of AKT will allow the development of peptide and small-molecule substrate-competitive covalent kinase inhibitors that incorporate additional substrate binding elements to increase selectivity and potency. This proof-of-principle study also provides a basis to apply this strategy to other kinases of the AGC and CAMK families.
• Novel poly(2-oxazoline)s with pendant <scp>l</scp>-prolinamide moieties as efficient organocatalysts for direct asymmetric aldol reaction
  作者：Yao Wang、Huifang Shen、Le Zhou、Fangyu Hu、Shoulei Xie、Liming Jiang

  DOI：10.1039/c6cy00448b

  日期：——

  bearing amino groups in the side-chains followed by amide coupling with N-Boc-L-proline then deprotection. The resultant L-prolinamido-functionalized polymers have proven to be significantly more active than their monomeric counterparts for the aldolisation of cyclic ketones with several substituted benzaldehydes under neat conditions. By using 15 mol% of the polymer as a catalyst, the direct aldol reaction

  聚（2-恶唑啉）负载的双功能有机催化剂已通过自下而上的方法制备，该方法涉及合成明确定义的侧链中带有氨基的聚（2-恶唑啉）前体，然后将酰胺与N -Boc偶联。-大号脯氨酸然后去保护。结果L已经证明，在纯净条件下，环戊酰胺基官能化的聚合物比其单体对应物具有明显更高的活性，可以在几种条件下用几种取代的苯甲醛将环酮醛醇缩合。通过使用15mol％的聚合物作为催化剂，直接的羟醛反应产物以高收率和良好的非对映和对映选择性被分离。基于圆二色性光谱分析，催化活性的增强可能与聚（2-恶唑啉）s的假肽支架的构象变化有关。另外，这些可溶性聚合物催化剂可通过在乙醚中沉淀五个催化循环而回收和再利用，而不会显着降低其效率。