2-Hydroxy-3-phenyl-(N-tert-butyl)-propionamid | 5510-44-1

• 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: 2-Hydroxy-3-phenyl-(N-tert-butyl)-propionamid
• CAS: 5510-44-1
• 化学式: C₁₃H₁₉NO₂
• 分子量: 221.299
• InChiKey: RTPXCWOSRBDUFQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16.0
• 可旋转键数：
  3.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  49.33
• 氢给体数：
  2.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  2-Hydroxy-3-phenyl-(N-tert-butyl)-propionamid 在 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 N-(tert-butyl)-2-oxo-3-phenylpropanamide
  参考文献：
  名称：

  Synthesis and biological evaluation of α-ketoamides as inhibitors of the Dengue virus protease with antiviral activity in cell-culture

  摘要：

  The development of small molecule inhibitors of the viral protease is of considerable interest for the treatment of emergent flaviviral diseases such as Dengue or West Nile fever. Until today little progress has been made in finding drug-like compounds that inhibit the protease and provide a starting point for lead optimization. We describe here the initial steps of a drug discovery effort that focused on the styryl pharmacophore, combined with a ketoamide function to serve as electrophilic trap for the catalytic serine. This resulted in a fragment-like lead compound with reasonable target affinity and good ligand efficiency, which was extensively modified to explore structure-activity relationships. Selected compounds were cross-tested against the West Nile virus protease and thrombin, indicating that selectivity for one or more flaviviral proteases can be achieved. Finally, the antiviral activity of several protease inhibitors was confirmed in a cell-culture model of Dengue virus replication. The SAR presented here may serve as starting point for further drug discovery efforts with the aim of targeting flaviviral proteases. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.05.015
• 作为产物：
  描述：

  1-benzyl-2-(tert-butylamino)-2-oxoethyl acetate 在 samarium diiodide 、 lithium chloride 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以52%的产率得到2-Hydroxy-3-phenyl-(N-tert-butyl)-propionamid
  参考文献：
  名称：

  SmI₂-Mediated Reduction of α-Functionalised Amides: Highly Enantiospecific Access to an Atropisomeric Amide

  摘要：

  SmI2或SmI2-LiCl混合物可用于还原α-取代酰胺，产率可高达85%，具体取决于酰胺的结构。该方法已应用于合成高度富含手性的对映异构体芳香胺体系，从(S)-O-乙酰乳酸开始。

  DOI：

  10.1055/s-1998-1838

文献信息

• On the direct use of CO₂in multicomponent reactions: introducing the Passerini four component reaction
  作者：Kelechukwu Nnabuike Onwukamike、Stéphane Grelier、Etienne Grau、Henri Cramail、Michael A. R. Meier

  DOI：10.1039/c8ra07150k

  日期：——

  isocyanide-based multicomponent reaction, the Passerini four component reaction (P-4CR), by replacing the carboxylic acid component of a conventional Passerini three component reaction (P-3CR) with an alcohol and CO2. Key to this approach is the use of a switchable solvent system, allowing the synthesis of a variety of α-carbonate-amides. The reaction was first investigated and optimized using butanol, isobutyraldehyde

  我们介绍了一种新颖的基于异氰化物的多组分反应，即 Passerini 四组分反应 (P-4CR)，通过用醇和 CO 2代替传统 Passerini 三组分反应 (P-3CR) 的羧酸组分。这种方法的关键是使用可切换的溶剂系统，允许合成各种 α-碳酸酯-酰胺。该反应首先使用丁醇、异丁醛、叔丁基异氰化物和CO 2进行研究和优化。研究的参数包括反应物当量、反应物浓度、溶剂、催化剂、催化剂浓度和 CO 2的影响压力。在其他参数中，醛的纯度及其氧化倾向是成功 P-4CR 的最关键参数之一。优化后，共合成了十二 (12) 种 P-4CR 化合物，转化率介于 16% 和 82% 之间，分离产率介于 18% 和 43% 之间。它们的结构通过 1 H 和13 C NMR、FT-IR 和高分辨率质谱 (ESI-MS) 得到证实。此外，P-4CR（α-羟基酰胺）的三 (3) 种水解产物被成功分离，产率在 23%
• Giraud-Clenet,D.; Anatol,J., Comptes Rendus des Seances de l'Academie des Sciences, Serie C: Sciences Chimiques, 1966, vol. 262, p. 224 - 227
  作者：Giraud-Clenet,D.、Anatol,J.

  DOI：——

  日期：——
• Synthesis and biological evaluation of α-ketoamides as inhibitors of the Dengue virus protease with antiviral activity in cell-culture
  作者：Christian Steuer、Christian Gege、Wolfgang Fischl、Karl H. Heinonen、Ralf Bartenschlager、Christian D. Klein

  DOI：10.1016/j.bmc.2011.05.015

  日期：2011.7

  The development of small molecule inhibitors of the viral protease is of considerable interest for the treatment of emergent flaviviral diseases such as Dengue or West Nile fever. Until today little progress has been made in finding drug-like compounds that inhibit the protease and provide a starting point for lead optimization. We describe here the initial steps of a drug discovery effort that focused on the styryl pharmacophore, combined with a ketoamide function to serve as electrophilic trap for the catalytic serine. This resulted in a fragment-like lead compound with reasonable target affinity and good ligand efficiency, which was extensively modified to explore structure-activity relationships. Selected compounds were cross-tested against the West Nile virus protease and thrombin, indicating that selectivity for one or more flaviviral proteases can be achieved. Finally, the antiviral activity of several protease inhibitors was confirmed in a cell-culture model of Dengue virus replication. The SAR presented here may serve as starting point for further drug discovery efforts with the aim of targeting flaviviral proteases. (C) 2011 Elsevier Ltd. All rights reserved.
• SmI₂-Mediated Reduction of <i>α</i>-Functionalised Amides: Highly Enantiospecific Access to an Atropisomeric Amide
  作者：Adam D. Hughes、Nigel S. Simpkins

  DOI：10.1055/s-1998-1838

  日期：1998.9

  SmI2 or SmI2-LiCl mixtures can be used to reduce α-functionalised amides in yields of up to 85% depending upon the amide structure. The method has been applied to the synthesis of an atropisomeric anilide system in highly enantioenriched form, starting with (S)-O-acetyl lactic acid.

  SmI2或SmI2-LiCl混合物可用于还原α-取代酰胺，产率可高达85%，具体取决于酰胺的结构。该方法已应用于合成高度富含手性的对映异构体芳香胺体系，从(S)-O-乙酰乳酸开始。