(S)-5-methylpyrrolidine-2,4-dione | 151004-17-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (S)-5-methylpyrrolidine-2,4-dione
• 英文别名: (5S)-5-methylpyrrolidine-2,4-dione
• CAS: 151004-17-0
• 化学式: C₅H₇NO₂
• 分子量: 113.116
• InChiKey: VKKNQZBZGSFRCA-VKHMYHEASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  8
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 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：

  (S)-5-methylpyrrolidine-2,4-dione 在 正丁基锂 、 双(三甲基硅烷基)氨基钾 作用下， 以 四氢呋喃 、 正己烷 、 甲苯 为溶剂， 反应 0.84h， 生成 9H-fluoren-9-ylmethyl N-[(2S)-1-[(2S)-3-ethoxy-2-methyl-5-oxo-2H-pyrrol-1-yl]-4-methyl-1-oxopentan-2-yl]carbamate
  参考文献：
  名称：

  Dipeptide Analogues Containing 4-Ethoxy-3-pyrrolin-2-ones

  摘要：

  Pyrrolidine-2,4-diones (1) are naturally occurring analogues of amino acids. We herein present a facile synthesis of N-acylated, O-alkylated pyrrolin-2-ones (2) in high yield and excellent enantiopurity. Molecular mechanics calculations suggest that the resulting dipeptide analogues adopt a linear, extended conformation.

  DOI：

  10.1021/ol060500i
• 作为产物：
  描述：

  苄氧羰基-L-丙氨酸 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 生成 (S)-5-methylpyrrolidine-2,4-dione
  参考文献：
  名称：

  Diastereofacial selectivity in reduction of chiral tetramic acids

  摘要：

  The reduction of (5S)-5-alkyl-2,4-dioxopyrrolidines, so-called tetramic acids, by NaBH4 gives only partial diastereofacial selectivity in the case of the N-substituted analogues 9f-i, unlike the carbamate derivatives 9a-3 which give the reduced cis-pyrrolidinones 10betaa-e. Increasing the steric hindrance of either the N- or C-5-substituents enhances the re-face selectivity. On the other hand, reduction of the heterobicyclic compound 9n leads to a dramatic reversal of the stereoselectivity. Preliminary calculations show that the N-atom of the ring is slightly pyramidalized; the direction of hydride addition could be a consequence of this finding.

  DOI：

  10.1021/jo00072a018

文献信息

• Bioactivity and Mode of Action of Bacterial Tetramic Acids
  作者：Martin Klapper、André Paschold、Shuaibing Zhang、Christiane Weigel、Hans-Martin Dahse、Sebastian Götze、Simona Pace、Stefanie König、Zhigang Rao、Lisa Reimer、Oliver Werz、Pierre Stallforth

  DOI：10.1021/acschembio.9b00388

  日期：2019.8.16

  antibacterial, antiproliferative, and cytotoxic activities. The length of the alkyl side chain and the nature of the amino acid residues within the tetramic acid moiety strongly affected activity, in particular against mycobacteria. The mode of action was shown to correlate with the ability of pyreudiones to act as protonophores. Removal of the acidic proton by methylation of pyreudione A resulted in

  微生物产生的3-酰基四酸显示出多种生物活性。吡啶二酮是从假单胞菌属细菌中分离出来的这类新成员。在这里，我们进行了结构-活性关系研究，并确定了它们的作用方式。开发了一种有效的仿生合成法来合成吡啶酮二酮。测试了吡啶酮及其合成类似物的杀螨，抑菌，抗增殖和细胞毒性活性。烷基侧链的长度和四氨基酸部分内氨基酸残基的性质强烈影响了活性，特别是抗分枝杆菌的活性。已显示作用方式与吡啶二酮充当质子体的能力相关。
• A Synthetic Approach to Diverse 3-Acyltetramic Acids via <i>O</i>- to <i>C</i>-Acyl Rearrangement and Application to the Total Synthesis of Penicillenol Series
  作者：Tetsuya Sengoku、Yuta Nagae、Yasuaki Ujihara、Masaki Takahashi、Hidemi Yoda

  DOI：10.1021/jo300527f

  日期：2012.5.4

  efficient approach to medicinally important α-branched 3-acyltetramic acids, the key reaction of O- to C- acyl rearrangement using α-amino-acid-derived 4-O-acyltetramic acids was extensively examined in the presence of various metal salts. Use of CaCl2 or NaI dramatically changed the results in the reaction efficiency and rapidly brought about the desired α-branched 3-acyltetramic acids in markedly

  为了有效地利用具有重要医学意义的α-支链3-酰基四酸，在各种金属盐存在下，广泛研究了使用α-氨基酸衍生的4- O-酰基四酸对O-进行C酰基重排的关键反应。。CaCl 2或NaI的使用显着改变了反应效率的结果，并以显着提高的产率迅速产生了所需的α-支化的3-酰基四酸。我们还讨论了重排条件下C5立体中心的差向异构化以及C3和C5的结构变异耐受性。除了先前在成功合成新的细胞毒性四酸青霉素A 1方面的成功之外，，这种方法也可以应用于青霉素A 2的第一次全合成。
• [EN] DUAL NAV1.2/5HT2A INHIBITORS FOR TREATING CNS DISORDERS<br/>[FR] INHIBITEURS DOUBLES DE NAV1.2/5HT2A POUR TRAITER DES TROUBLES DU SNC
  申请人：SUNOVION PHARMACEUTICALS INC

  公开号：WO2018026371A1

  公开（公告）日：2018-02-08

  Compounds of formula I: I are disclosed, as are pharmaceutical compositions containing such compounds. Methods of treating neurological or psychiatric disorders in a patient in need are also disclosed. Such disorders include depression, bipolar disorder, pain, schizophrenia, obsessive compulsive disorder, addiction, social disorder, attention deficit hyperactivity disorder, an anxiety disorder, autism, a cognitive impairment, or a neuropsychiatric symptom such as apathy, depression, anxiety, psychosis, aggression, agitation, impulse control disorders, and sleep disorders in neurological disorders such as Alzheimer's and Parkinson's diseases.

  公开了化学式I的化合物，以及含有这些化合物的药物组合物。还公开了治疗患有神经系统或精神障碍的患者的方法。这些障碍包括抑郁症、躁郁症、疼痛、精神分裂症、强迫症、成瘾、社交障碍、注意力缺陷多动障碍、焦虑障碍、自闭症、认知障碍，或神经精神症状，如冷漠、抑郁、焦虑、精神病、攻击性、激动、冲动控制障碍，以及在神经系统疾病如阿尔茨海默病和帕金森病中的睡眠障碍。
• Structure-Activity Relationships of Precursors and Analogs of Natural 3-Enoyl-tetramic Acids
  作者：Bertram Barnickel、Frances Bayliffe、Randi Diestel、Karl Kempf、Sabine Laschat、Steffen Pachali、Florenz Sasse、Andrea Schlenk、Rainer Schobert

  DOI：10.1002/cbdv.201000179

  日期：2010.12

  β-hydroxy-octatrienoyl amide precursor to aburatubolactam also exhibited distinct activity with an IC₅₀ (120 h) value of <2.5 μM. The length of 3-oligoenoyl residues had little influence on the anticancer activity, but 3-alka-oligoenoyl tetramic acids were far more efficacious than their 3-(4-methoxycinnamoyl) congeners. N-H-3-acyltetramic acids were generally more active than their N-Me or N-Boc analogs, unless further

  制备的片段和合成前体与大环3-酰基四酸（= 3-酰基-1,5-二氢-4-羟基-2H-吡咯-2-酮）烟酰胺内酰胺和大环蛋白A以及其他类似物在环杂原子（N，O，S）中的残基（N，O，S）和N（1），C（3）和C（5）处的残基进行了细胞毒性和抗菌作用测试。在体外针对各种肿瘤细胞系的抗癌活性不一定需要完整的吡咯烷-2,4-二酮环。环丁草内酰胺的无环β-羟基-八碳三烯酰基酰胺前体也表现出独特的活性，IC 50（120 h）值<2.5μM。3-寡烯酰基残基的长度对抗癌活性几乎没有影响，但是3-碱-寡烯酰基四酸比其3-（4-甲氧基肉桂酰基）同类物更有效。NH-3-酰基丁二酸通常比其N-Me或N-Boc类似物更具活性，除非另外的极性基团需要增加亲脂性以充分摄取。与同等取代的四酸相比，Tetronic和thiotetronic酸在癌细胞中的抗增殖能力要低得多。
• Extended Piperidine–Piperidinone Protein Interface Mimics
  作者：Dongyue Xin、Arjun Raghuraman、Kevin Burgess

  DOI：10.1021/acs.joc.5b00300

  日期：2015.5.1

  dichroism (CD) study. Thus, an estimate of 36 Å for the N-to-C distance of a typical conformation of the penta(piperidinone–piperidine) was made. CD spectra of four progressively longer oligomers allowed assignment of elipticity changes around 300 nm that can be attributed to increased conformational ordering of the longer oligomers in solution.

  极简主义的结构H和I被设计为蛋白质界面模拟物。这些化学型的特性是：（i）比常规肽更高的刚性；（ii）较不易产生疏水聚集效应的手性和非平面杂环骨架；以及（iii）具有与天然氨基酸相对应的各种侧链的制备潜力酸。然而，在低聚（吡咯烷酮-哌啶）的H中间体中，易合成差向异构体。确定了这种差向异构的起源，然后研究集中在寡聚（哌啶酮-哌啶）化合物Ⅰ上。模拟我是通过迭代耦合准备的。一个五（哌啶酮-哌啶）以此方式制备。对该五聚体的一系列较低的同系物进行了结晶和研究（单晶X射线），并将其中的四个用于圆二色性（CD）研究。因此，对五（哌啶酮-哌啶）典型构象的N-C距离进行了估计，结果约为36Å。四种逐渐变长的低聚物的CD光谱允许分配约300 nm的椭圆率变化，这可归因于溶液中较长的低聚物的构象排列增加。