(R)-2-[(S)-2,5-dioxo-1-phenylpyrrolidin-3-yl]-2-phenylpropanal | 1380095-44-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (R)-2-[(S)-2,5-dioxo-1-phenylpyrrolidin-3-yl]-2-phenylpropanal
• 英文别名: (2R)-2-[(3S)-2,5-dioxo-1-phenylpyrrolidin-3-yl]-2-phenylpropanal
• CAS: 1380095-44-2
• 化学式: C₁₉H₁₇NO₃
• 分子量: 307.349
• InChiKey: CDGGPFPLQSFJGF-APWZRJJASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  54.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  N-苯基马来酰亚胺 、 2-苯基丙醛 在 苏氨酸叔丁酯 、 potassium hydroxide 作用下， 以 二氯甲烷 为溶剂， 反应 10.03h， 生成 (R)-2-[(S)-2,5-dioxo-1-phenylpyrrolidin-3-yl]-2-phenylpropanal
  参考文献：
  名称：

  非共价双功能有机催化剂：强大的工具，用于连续的第四-第三系立体生碳的形成，范围和对映选择性的起源

  摘要：

  依靠商业上可买到的催化剂构件的组装，已经实现了具有无与伦比的底物多样性的高度立体控制的季碳（所有碳取代的）形成。例如，三组分催化剂体系的原位组装允许将α-支链醛加成到硝基烯烃或马来酰亚胺亲电试剂中（Michael产品），而将α-支链醛加成可以得到曼尼希反应产物。观察到非常高的收率，在18个实例中，有15个实例的96-99％ee被观察到。使用外消旋的α-支链醛，可以通过高效的原位动态动力学拆分在高非对映异构体和对映体过量（八个实例）中形成两个连续的（四级-三级）立体中心，尤其是解决了已知的马来酰亚胺亲电试剂的缺点。该方法具有实用价值，仅需要1.2当量的醛，每种催化剂组分的负载量为5.0 mol％，例如O- t Bu- L-苏氨酸（O- t Bu- L- Thr），磺酰胺，DMAP或O-吨BU-大号-Thr，KOH，和室温下的反应。作为亮点，乙基异戊醛（7公开了添加），提供迄今已知的最拥挤的含

  DOI：

  10.1002/chem.201103005

文献信息

• Primary Amine–2-Aminopyrimidine Chiral Organocatalysts for the Enantioselective Conjugate Addition of Branched Aldehydes to Maleimides
  作者：Carmen Nájera、Enrique Gómez-Bengoa、Pascuala Vízcaíno-Milla、José Sansano、Béla Fiser

  DOI：10.1055/s-0034-1380718

  日期：——

  corresponding succinimides in good yields and enantioselectivities. DFT calculations support the stereochemical results and the role played by the solvents. Chiral primary amines containing the (R,R)- and (S,S)-trans-cyclohexane-1,2-diamine scaffold and a pyrimidin-2-yl unit are synthesized and used as general organocatalysts for the Michael reaction of α-branched aldehydes to maleimides. The reaction

  摘要 合成含有（R，R）-和（S，S）-反式-环己烷-1,2-二胺骨架和嘧啶-2-基单元的手性伯胺，并将其用作α-的迈克尔反应的一般有机催化剂支链醛成马来酰亚胺。该反应在10℃下在N，N-二甲基甲酰胺水溶液中以10mol％的有机催化剂负载量和己二酸作为助催化剂进行，以良好的产率和对映选择性提供了相应的琥珀酰亚胺。DFT计算支持立体化学结果和溶剂的作用。 合成含有（R，R）-和（S，S）-反式-环己烷-1,2-二胺骨架和嘧啶-2-基单元的手性伯胺，并将其用作α-的迈克尔反应的一般有机催化剂支链醛成马来酰亚胺。该反应在10℃下在N，N-二甲基甲酰胺水溶液中以10mol％的有机催化剂负载量和己二酸作为助催化剂进行，以良好的产率和对映选择性提供了相应的琥珀酰亚胺。DFT计算支持立体化学结果和溶剂的作用。
• Noncovalent Bifunctional Organocatalysts: Powerful Tools for Contiguous Quaternary-Tertiary Stereogenic Carbon Formation, Scope, and Origin of Enantioselectivity
  作者：Thomas C. Nugent、Abdul Sadiq、Ahtaram Bibi、Thomas Heine、Lei Liu Zeonjuk、Nina Vankova、Bassem S. Bassil

  DOI：10.1002/chem.201103005

  日期：2012.3.26

  observed. Using racemic α‐branched aldehydes, two contiguous (quaternary–tertiary) stereogenic centers can be formed in high diastereo‐ and enantiomeric excess (eight examples) via an efficient in situ dynamic kinetic resolution, solving a known shortcoming for maleimide electrophiles in particular. The method is of practical value, requiring only 1.2 equiv of the aldehyde, a 5.0 mol % loading of each catalyst

  依靠商业上可买到的催化剂构件的组装，已经实现了具有无与伦比的底物多样性的高度立体控制的季碳（所有碳取代的）形成。例如，三组分催化剂体系的原位组装允许将α-支链醛加成到硝基烯烃或马来酰亚胺亲电试剂中（Michael产品），而将α-支链醛加成可以得到曼尼希反应产物。观察到非常高的收率，在18个实例中，有15个实例的96-99％ee被观察到。使用外消旋的α-支链醛，可以通过高效的原位动态动力学拆分在高非对映异构体和对映体过量（八个实例）中形成两个连续的（四级-三级）立体中心，尤其是解决了已知的马来酰亚胺亲电试剂的缺点。该方法具有实用价值，仅需要1.2当量的醛，每种催化剂组分的负载量为5.0 mol％，例如O- t Bu- L-苏氨酸（O- t Bu- L- Thr），磺酰胺，DMAP或O-吨BU-大号-Thr，KOH，和室温下的反应。作为亮点，乙基异戊醛（7公开了添加），提供迄今已知的最拥挤的含
• An Asymmetric Michael Addition of α,α-Disubstituted Aldehydes to Maleimides Leading to a One-Pot Enantioselective Synthesis of Lactones Catalyzed by Amino Acids
  作者：Christoforos G. Kokotos

  DOI：10.1021/ol4008662

  日期：2013.5.17

  A cheap and fast construction of both enantiomers of substituted succinimides is reported. α- or β-amino acids, such as β-phenylalanine and α-tert-butyl aspartate, were found to be efficient organocatalysts for the reaction between α,α-disubstituted aldehydes and maleimides. Products containing contiguous quaternary-tertiary stereogenic centers are obtained in high to quantitative yields and excellent

  据报道便宜和快速地构建了取代的琥珀酰亚胺的两种对映体。发现α-或β-氨基酸，如β-苯丙氨酸和α-叔丁基天冬氨酸，是用于α，α-二取代的醛与马来酰亚胺之间反应的有效有机催化剂。使用低催化剂负载量（0.5-3.5％），可以以高产量到定量产量和出色的选择性获得包含连续的四级-三级立体异构中心的产品。最后，描述了一锅高效内酯的不对称合成。
• Organocatalytic enantioselective conjugate addition of aldehydes to maleimides in deep eutectic solvents
  作者：Jesús Flores-Ferrándiz、Rafael Chinchilla

  DOI：10.1016/j.tetasy.2016.12.009

  日期：2017.2

  The conjugate enantioselective addition of aldehydes, mainly alpha,alpha-disubstituted, to maleimides leading to enantioenriched succinimides, has been achieved in recyclable deep eutectic solvents at room temperature. Enantiomerically pure carbamate-monoprotected trans-cyclohexane-1,2-diamines are used as organocatalysts, affording high yields and up to 94% ee of the final succinimides. The product can be extracted from the deep eutectic solvent, which retains the chiral organocatalyst, allowing both the solvent and catalyst to be reused. (C) 2016 Elsevier Ltd. All rights reserved.
• <p>Comparative Cholinesterase, α-Glucosidase Inhibitory, Antioxidant, Molecular Docking, and Kinetic Studies on Potent Succinimide Derivatives</p>
  作者：Ashfaq Ahmad、Farhat Ullah、Abdul Sadiq、Muhammad Ayaz、Muhammad Saeed Jan、Muhammad Shahid、Abdul Wadood、Fawad Mahmood、Umer Rashid、Riaz Ullah、Muhammad Umar Khayam Sahibzada、Ali S Alqahtani、Hafiz Majid Mahmood

  DOI：10.2147/dddt.s237420

  日期：——

  Introduction: The current study was designed to synthesize derivatives of succinimide and compare their biological potency in anticholinesterase, alpha-glucosidase inhibition, and antioxidant assays.Methods: In this research, two succinimide derivatives including (S)-1-(2,5-dioxo-1-phenylpyrrolidin-3-yl) cyclohexanecarbaldehyde (Compound 1) and (R)-2-((S)-2,5-dioxo-1-phenylpyrrolidin-3-yl)-2-phenylpropanal (Compound 2) were synthesized using Michael addition. Both the compounds, ie, 1 and 2 were evaluated for in-vitro acetylcholinesterase (AChE), buty Ictcholinesterase (BChE), antioxidant, and alpha-glucosidase inhibitory potentials. Furthermore, molecular docking was performed using Molecular Operating Environment (MOE) to explore the binding mode of both the compounds against different enzymes. Lineweaver-Burk plots of enzyme inhibitions representing the reciprocal of initial enzyme velocity versus the reciprocal of substrate concentration in the presence of synthesized compounds and standard drugs were constructed using Michaelis-Menten kinetics.Results: In AChE inhibitory assay, compounds 1 and 2 exhibited IC50 of 343.45 and 422.98 mu M, respectively, against AChE enzyme. Similarly, both the compounds showed IC50 of 276.86 and 357.91 mu M, respectively, against BChE enzyme.Compounds 1 and 2 displayed IC50 of 157.71 and 471.79 mu M against alpha-glucosidase enzyme, respectively. In a similar pattern, compound 1 exhibited to be more potent as compared to compound 2 in all the three antioxidant assays. Compound 1 exhibited IC50 values of 297.98, 332.94, and 825.92 mu M against DPPH, ABTS, and H2O2 free radicals, respectively. Molecular docking showed a triple fold in the AChE and BChE activity for compound 1 compared with compound 2. The compound 1 revealed good interaction against both the AChE and BChE enzymes which revealed the high potency of this compound compared to compound 2.Conclusion: Both succinimide derivatives exhibited considerable inhibitory activities against cholinesterases and alpha-glucosidase enzymes. Of these two, compound 1 revealed to be more potent against all the in-vitro targets which was supported by molecular docking with the lowest binding energies. Moreover, compound 1 also proved to have antiradical properties.