(E)-N-benzyl-2-oxo-4-phenylbut-3-enamide

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-N-benzyl-2-oxo-4-phenylbut-3-enamide
• 化学式: C₁₇H₁₅NO₂
• 分子量: 265.312
• InChiKey: BQFAUXPRTQQFJL-VAWYXSNFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  46.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (E)-N-benzyl-2-oxo-4-phenylbut-3-enamide 在 bis(1,5-cyclooctadiene)diiridium(I) dichloride 、 C₃₂H₃₇FeN₂OP 、 氢气 、 potassium hydroxide 作用下， 以 1,2-二氯乙烷 为溶剂， 20.0 ℃ 、5.07 MPa 条件下， 反应 12.0h， 以94%的产率得到
  参考文献：
  名称：

  铱/f-Amphox 催化的苯乙烯基乙醛酰胺的不对称氢化

  摘要：

  我们报告了用于制备手性高苯丙氨酸衍生物的铱催化不对称氢化反应。在铱/f-amphox 络合物的催化下，苯乙烯基乙醛酰胺的不对称氢化顺利进行，转化率高达 10,000，ee 高达 98%。该方法已成功应用于苯那普利片段的合成，这是一种用于治疗高血压的药物。

  DOI：

  10.1055/s-0037-1609623
• 作为产物：
  描述：

  N-benzyl-2-hydroxy-4-phenylbut-3-enamide 在 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以17%的产率得到(E)-N-benzyl-2-oxo-4-phenylbut-3-enamide
  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

文献信息

• Enantioselective Copper-Catalyzed Conjugate Addition of Trimethylaluminum to β,γ-Unsaturated α-Ketoamides: Efficient Access to γ-Methyl-Substituted Carbonyl Compounds
  作者：Sylvie Goncalves-Contal、Ludovic Gremaud、Alexandre Alexakis

  DOI：10.1002/anie.201306541

  日期：2013.11.25

  4‐adducts were obtained with perfect 1,4‐regioselectivity and good to excellent yields and ee values. The potential synthetic utility of the methodology was highlighted by preparation of γ‐methyl‐substituted carbonyls, key synthons to many natural products. binap=2,2′‐bis(diphenylphosphino)‐1,1′‐binaphthyl, TC=thiophene carboxylate.

  完美图片：通过使用三甲基铝试剂和β，γ-不饱和α-酮酰胺，可获得1,4-加合物，具有完美的1,4-区域选择性，并具有极佳的收率和ee 值。通过制备γ-甲基取代的羰基化合物（许多天然产物的关键合成子），突出了该方法的潜在合成效用。binap = 2,2'-双（二苯基膦基）-1,1'-联萘基，TC =噻吩羧酸盐。
• Asymmetric Aerobic Oxidation of α-Hydroxy Acid Derivatives Catalyzed by Reusable, Polystyrene-Supported Chiral N-Salicylidene Oxidovanadium tert-Leucinates
  作者：Santosh B. Salunke、N.Seshu Babu、Chien-Tien Chen

  DOI：10.1002/adsc.201100062

  日期：2011.5

  The direct immobilization of two different C‐5‐propargyl ether‐modified, chiral N‐salicylidene vanadyl(V) tert‐leucinates onto 4‐azidomethyl‐substituted polystyrene by click chemistry was examined. Among the eight different solvents investigated, the resulting polystyrene‐supported catalysts promote the asymmetric, aerobic oxidation of α‐hydroxy (thio)esters and amides with enantioselectivities of

  通过点击化学方法研究了将两种不同的C-5-炔丙基醚改性的手性N-水杨基亚烷基钒（V）叔亮氨酸酯直接固定在4-叠氮基甲基取代的聚苯乙烯上的方法。在所研究的八种不同溶剂中，所得的聚苯乙烯负载催化剂促进了α-羟基（硫代）酯和酰胺的不对称，好氧氧化，其在氯仿中的对映选择性高达99％ee（选择性高达41）。这些聚苯乙烯负载的催化剂可以很容易地通过过滤回收，并至少连续四次重复使用，而不会损失反应性和对映选择性。
• NHC-mediated enantioselective formal [4 + 2] cycloadditions of alkylarylketenes and β,γ-unsaturated α-ketocarboxylic esters and amides
  作者：Stuart M. Leckie、T. Bruce Brown、David Pryde、Tomas Lebl、Alexandra M. Z. Slawin、Andrew D. Smith

  DOI：10.1039/c3ob40424b

  日期：——

  Chiral N-heterocyclic carbenes (NHCs) promote the asymmetric formal [4 + 2] cycloaddition of alkylarylketenes with β,γ-unsaturated α-ketocarboxylic esters and amides. Divergent diastereoselectivity is observed in this process, with γ-aryl-β,γ-unsaturated α-ketocarboxylic esters and amides giving preferentially syn-dihydropyranones (up to 68 : 32 dr syn : anti, up to 98% ee), while γ-alkyl-derivatives generate

  手性N-杂环卡宾（NHC）促进烷基芳基烯酮与β，γ-不饱和α-酮羧酸酯和酰胺的不对称形式[4 + 2]环加成。在此过程中观察到不同的非对映选择性，其中γ-芳基-β，γ-不饱和α-酮羧酸酯和酰胺优先提供顺-二氢吡喃酮（高达68:32 dr syn  ：  anti，高达98％ee），而γ-烷基衍生物生成抗二氢吡喃酮（高达18:82 dr syn  ：  anti，高达75％ee）。
• Highly Efficient Synthesis of trans-β,γ-Unsaturated α-Keto Amides
  作者：Thierry Constantieux、Jean Rodriguez、Christophe Allais

  DOI：10.1055/s-0029-1216869

  日期：2009.8

  A highly efficient, metal-free, and selective access to trans-β,γ-unsaturated α-keto amides is described via peptidic coupling, involving easy to prepare trans-β,γ-unsaturated α-keto acids and commercially available amines. β,γ-unsaturated α-keto amide - α-keto acid - amine - peptidic coupling - Michael acceptor

  通过肽偶联描述了高效，无金属且选择性地获得反-β，γ-不饱和α-酮酰胺的方法，涉及容易制备反-β，γ-不饱和α-酮酸和市售胺。 β，γ-不饱和α-酮酰胺-α-酮酸-胺-肽偶联-Michael受体
• Direct Organocatalytic Construction of Bicyclo[3.2.1]octanes by Domino Michael/Aldol Reaction with β,γ-Unsaturated 1,2-Keto Amides
  作者：Alexandre Alexakis、Alice Lefranc、Laure Guénée、Sylvie Goncalves-Contal

  DOI：10.1055/s-0034-1378901

  日期：——

  A direct construction of bicyclo[3.2.1]octanes by an organocatalytic domino Michael/Aldol reaction of cyclic 1,3-keto esters with β,γ-unsaturated 1,2-keto amides is reported. Formation of a precipitate corresponding to the racemic co-crystals of the bicyclic compound was observed in toluene, whereas a homogeneous solution was obtained in dichloromethane. Preliminary mechanistic investigations on the

  报道了通过环状 1,3-酮酯与 β,γ-不饱和 1,2-酮酰胺的有机催化多米诺迈克尔/羟醛反应直接构建双环 [3.2.1] 辛烷。在甲苯中观察到对应于双环化合物的外消旋共晶的沉淀物的形成，而在二氯甲烷中得到均相溶液。对系统可逆性的初步机械研究可以提高选择性（>20:1 dr，73% ee）。双环化合物的相对构型通过X射线晶体结构分析确定。