(E)-3-benzylidenepiperidin-2-one | 53031-80-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (E)-3-benzylidenepiperidin-2-one
• 英文别名: 3-Benzylidene-2-piperidinone；(3E)-3-benzylidenepiperidin-2-one
• CAS: 53031-80-4
• 化学式: C₁₂H₁₃NO
• 分子量: 187.241
• InChiKey: NGJPBMMZWJHTAD-PKNBQFBNSA-N

物化性质

• 沸点：
  407.8±38.0 °C(Predicted)
• 密度：
  1.122±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (E)-3-benzylidenepiperidin-2-one 在 palladium on activated charcoal 吡啶 、 4-二甲氨基吡啶 、 potassium osmate(VI) 、 AD-mix-α 、 甲基磺酰胺 、 氢气 、 溶剂黄146 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙醇 、 水 、 叔丁醇 为溶剂， 20.0 ℃ 、344.74 kPa 条件下， 生成 tert-butyl 2-[(3R)-3-(cyclohexylmethyl)-3-hydroxy-2-oxopiperidin-1-yl]acetate
  参考文献：
  名称：

  Asymmetric synthesis of novel quaternary α-Hydroxy-δ-lactam dipeptide surrogates

  摘要：

  Application of the Sharpless AD protocol to a series of alpha-(E)-benzylidene-delta-lactam precursors followed by selective deoxygenation provided efficient synthetic routes to the chiral quaternary alpha-hydroxy-gamma-lactam derivatives 4 and 5. These functionalized intermediates and the diol precursors 3 are regarded as novel types of D-Phe-Pro dipeptide surrogates that are useful as enzyme active site probes. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00448-5
• 作为产物：
  描述：

  哌啶酮 在 4-二甲氨基吡啶 、 三氟乙酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 10.0h， 生成 (E)-3-benzylidenepiperidin-2-one
  参考文献：
  名称：

  设计与合成 HDAC 抑制剂，通过改善代谢稳定性和药代动力学特征来增强弥漫性大 B 细胞淋巴瘤的治疗效果

  摘要：

  组蛋白去乙酰化酶 (HDAC) 是临床验证和有吸引力的人类癌症表观遗传药物靶点。迄今为止，有几种HDAC抑制剂已被批准用于癌症治疗，但由于HDAC抑制剂的药代动力学、生物利用度和选择性较差，临床应用受到限制，其中大多数需要与其他药物联合使用才能达到更好的效果。在这里，我们描述了我们为发现一系列新的内酰胺衍生物作为选择性 HDAC 抑制剂所做的努力。密集的结构修饰导致化合物24g被鉴定为最活跃的 I 类 HDAC 抑制剂，以及令人满意的体外代谢稳定性 (t 1/2, 人类 = 797 分钟) 和理想的口服生物利用度 (F = 92%)。更重要的是，化合物24g在TMD-8异种移植模型（TGI = 77%）中显示出良好的抗肿瘤功效，且无明显毒性。这些结果表明 I 类 HDAC 抑制剂可能潜在地用于治疗某些弥漫性大 B 细胞淋巴瘤疗法。

  DOI：

  10.1016/j.ejmech.2021.114049

文献信息

• SpinPhox/Iridium(I)-Catalyzed Asymmetric Hydrogenation of Cyclic α-Alkylidene Carbonyl Compounds
  作者：Xu Liu、Zhaobin Han、Zheng Wang、Kuiling Ding

  DOI：10.1002/anie.201309521

  日期：2014.2.10

  cyclic carbonyl compounds bearing an α‐chiral carbon center are of interest in pharmaceutical sciences and asymmetric synthesis. Herein, SpinPhox/IrI catalysts have been demonstrated to be highly enantioselective in the asymmetric hydrogenation of the CC bonds in the exocyclic α,β‐unsaturated cyclic carbonyls, including a broad range of α‐alkylidene lactams, unsaturated cyclic ketones, and lactones. It

  带有α-手性碳中心的旋光中型环状羰基化合物在制药科学和不对称合成中引起人们的兴趣。在本文中，SpinPhox / Ir I催化剂在环外α，β-不饱和环状羰基化合物（包括各种α-亚烷基内酰胺，不饱和环状酮）中的CC键的不对称氢化中被证明具有高度对映选择性。内酯。值得注意的是，该方法可以成功地用于具有六元或七元环的具有挑战性的α-烷基亚内酰胺底物的不对称氢化，从而提供相应的具有α-手性碳中心的旋光羰基化合物，其对映体过量通常非常好（高达ee的98％ ）。该协议的合成用途还已在抗炎药洛索洛芬及其类似物以及生物学上重要的ε-氨基己酸衍生物的不对称合成中得到证明。
• Iridium‐Catalyzed Highly Enantioselective Hydrogenation of Exocyclic α,β‐Unsaturated Carbonyl Compounds
  作者：Fengtao Tian、Dongmei Yao、Yuanyuan Liu、Fang Xie、Wanbin Zhang

  DOI：10.1002/adsc.201000185

  日期：2010.10.9

  By using the iridium complex of a phosphine-oxazoline ligand with an axis-unfixed biphenyl backbone, a highly enantioselective hydrogenation of the CC bond of exocyclic α,β-unsaturated carbonyl compounds to afford α-chiral cyclic ketones, lactones and lactams was developed.

  通过使用膦-恶唑啉配体的铱配合物和未固定轴联苯骨架，开发了环外α，β-不饱和羰基化合物的CC键的高度对映选择性氢化，从而提供了α-手性环酮，内酯和内酰胺。
• Enantioselective Synthesis of α-Chiral Amides by Catalytic Hydrogenation with Iridium N,P-Complexes
  作者：Bram B. C. Peters、Norman Birke、Pher G. Andersson、Luca Massaro

  DOI：10.1055/s-0042-1751399

  日期：——

  The catalytic asymmetric hydrogenation of olefins constitutes a powerful method for the preparation of chiral compounds. A series of prochiral unsaturated amides were efficiently reduced with high enantioselectivities by means of an iridium N,P-complex-catalyzed hydrogenation. Its application in the synthesis of fenpropidin and the possibility of using isomeric mixtures of starting materials are attractive

  烯烃的催化不对称氢化是制备手性化合物的有效方法。通过铱 N,P 络合物催化氢化，一系列前手性不饱和酰胺以高对映选择性有效还原。它在fenpropidin 合成中的应用以及使用起始原料的异构混合物的可能性是该方法的吸引人的特征。
• Enantioselective 1,3-Dipolar Cycloadditions of α-Methylene Lactams to Construct Spirocycles
  作者：Yuji Nishiura、Kevin J. Gonzalez、Alexander Q. Cusumano、Brian M. Stoltz

  DOI：10.1021/acs.orglett.3c01978

  日期：2023.9.8

  compounds. However, there is a need for efficient methods for their enantioselective construction. We report a method for the asymmetric 1,3-dipolar cycloaddition of diazoacetates or nitrile oxides with α-methylene lactams to prepare chiral spirocyclic heterocycles. The methodology is high yielding (up to 91% yield) and enantioselective (up to 89% ee) for a wide range of N-substituents and 6- and 7-membered

  螺环支架是重要的基序，因为它们有可能对药物化合物产生有利的作用。然而，需要有效的方法来构建它们的对映选择性。我们报道了一种重氮乙酸酯或氧化腈与α-亚甲基内酰胺进行不对称1,3-偶极环加成制备手性螺环杂环的方法。该方法对于多种N取代基以及 6 元环和 7 元环内酰胺底物具有高产率（高达 91% 产率）和对映选择性（高达 89% ee）。
• Natural α-methylenelactam analogues: Design, synthesis and evaluation of α-alkenyl-γ and δ-lactams as potential antifungal agents against Colletotrichum orbiculare
  作者：Wang Delong、Wang Lanying、Wu Yongling、Song Shuang、Feng Juntao、Zhang Xing

  DOI：10.1016/j.ejmech.2017.02.050

  日期：2017.4

  In our continued efforts to improve the potential utility of the alpha-methylene-gamma-lactone scaffold, 62 new and 59 known natural alpha-methylenelactam analogues including alpha-methylene-gamma- lactams, alpha-arylidene- gamma and delta-lactams, and 3-arylideneindolin-2-ones were synthesized as the bioisosteric analogues of the amethylenelactone scaffold. The results of antifungal and cytotoxic activity indicated that among these derivatives compound (E)-1-(2, 6-dichlorobenzyl)-3-(2-fluorobenzylidene) pyrrolidin-2-one (Py51) possessed good selectivity with the highest antifungal activity against Colletotrichum orbiculare with IC50 - 10.4 mu M but less cytotoxic activity with IC50 - 141.2 mu M (against HepG2 cell line) and 161.2 mu M ( against human hepatic L02 cell line). Ultrastructural change studies performed by transmission electron microscope showed that Py51 could cause important cell morphological changes in C. orbiculare, such as plasma membrane detached from cell wall, cell wall thickening, mitochondria disruption, a dramatic increase in vacuolation, and eventually a complete loss in the integrity of organelles. Significantly, mitochondria appeared one of the primary targets, as confirmed by their remarkably aberrant morphological changes. Analysis of structureeactivity relationships revealed that incorporation of the aryl group into the alpha-exo methylene and the N-benzyl substitution increased the activity. Meanwhile, the alpha-arylidene-gamma-lactams have superiority in selectivity over the 3-arylideneindolin-2-ones. Based on the results, the N- benzyl substituted a-(2-fluorophenyl)-gamma-lactam was identified as the most promising natural- based scaffold for further discovering and developing improved crop- protection agents. (c) 2017 Elsevier Masson SAS. All rights reserved.