(E)-3-phenylmethylene-2-pyrrolidinone | 1859-41-2

• 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: (E)-3-phenylmethylene-2-pyrrolidinone
• 英文别名: (E)-3-benzylidenepyrrolidin-2-one；(E)-3-Benzyliden-2-pyrrolidon；3-Benzyliden-2-pyrrolidon；3-Benzylidenepyrrolidin-2-one；(3E)-3-benzylidenepyrrolidin-2-one
• CAS: 1859-41-2；50908-72-0
• 化学式: C₁₁H₁₁NO
• 分子量: 173.214
• InChiKey: OMARMBRFLQVQJA-CSKARUKUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 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-phenylmethylene-2-pyrrolidinone 在 水 、 sodium hydride 、 potassium iodide 、 sodium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 (E)-4-((3-benzylidene-2-oxopyrrolidin-1-yl)methyl)benzoic acid
  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
• 作为产物：
  描述：

  (EZ)-4-Benzamido-2-benzylidenbuttersaeureethylester 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以73%的产率得到(E)-3-phenylmethylene-2-pyrrolidinone
  参考文献：
  名称：

  Stamm; Baumann, Pharmazie, 1999, vol. 54, # 12, p. 885 - 888

  摘要：

  DOI：

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。
• Synthesis and chemistry of new spiro-Δ1-pyrazoline
  作者：Nesrine Louhichi、Amel Houas、Naoufel Ben Hamadi、Moncef Msaddek

  DOI：10.1002/jhet.827

  日期：2012.3

  spiroheterocycles, we found that the reaction of 2‐diazopropane with (E)‐α‐arylidenepyrrolin‐2‐one, (E)‐α‐arylidene‐γ‐butyrolactone, and (E)‐arylidene‐N‐arylsuccinimide derivatives produced spiro‐Δ1‐pyrazolines. The photolysis of Δ1‐pyrazolines has led to cyclopropanes. The structures of the obtained adducts have been assigned by means of spectroscopic measurements. J. Heterocyclic Chem., (2011).

  在螺环杂环的合成和化学探索中，我们发现2-重氮丙烷与（E）-α-亚芳基吡咯啉-2-酮，（E）-α-亚芳基-γ-丁内酯和（E）-亚芳基-萘酮的反应ñ -arylsuccinimide衍生物产生螺-Δ 1个-pyrazolines。Δ的光解1 -pyrazolines导致环丙烷。所获得的加合物的结构已经通过光谱测量确定。J.杂环化​​学。（2011）。
• 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.
• Synthesis of substituted (α-methylene lactams by rhodium catalysed carbonylation of acetylenic amines
  作者：Eva M. Campi、J.Michael Chong、W.Roy Jackson、Marcel Van Der Schoot

  DOI：10.1016/s0040-4020(01)86969-6

  日期：1994.2

  Reactions of gamma- and beta-aminoalkynes, (2) and (5) with hydrogen and carbon monoxide in the presence of rhodium catalysts give substituted alpha-methylene-2-piperidinones (7) and 2-pyrrolidinones (11).