5-(1-hydroxy-2-(naphthalen-1-yl)ethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione | 288270-18-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 5-(1-hydroxy-2-(naphthalen-1-yl)ethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione
• 英文别名: 5-[1-hydroxy-2-(1-naphthyl)ethylidene]-2,2-dimethyl-1,3-dioxane-4,6-dione；5-(1-Hydroxy-2-naphthalen-1-ylethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione
• CAS: 288270-18-8
• 化学式: C₁₈H₁₆O₅
• 分子量: 312.322
• InChiKey: JPNDJEQNRSOARA-UHFFFAOYSA-N

物化性质

• 熔点：
  104 °C (decomp)
• 沸点：
  578.9±50.0 °C(Predicted)
• 密度：
  1.314±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-(1-hydroxy-2-(naphthalen-1-yl)ethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione 在 sodium methylate 、 间氯过氧苯甲酸 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 49.0h， 生成 methyl 2-methyl-8-(naphthalen-1-ylmethyl)-6-oxo-9-(3-(trifluoromethyl)phenyl)-3,4-dihydro-2H,6H-pyrido[1,2-e][1,2,5]thiadiazine-4-carboxylate 1,1-dioxide
  参考文献：
  名称：

  [EN] INHIBITORS OF MICROBIALLY INDUCED AMYLOID
  [FR] INHIBITEURS D'AMYLOÏDE INDUITE PAR VOIE MICROBIENNE

  摘要：

  公开号：

  WO2021142333A3
• 作为产物：
  描述：

  1-萘乙酸 在 4-二甲氨基吡啶 、 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 5.5h， 生成 5-(1-hydroxy-2-(naphthalen-1-yl)ethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione
  参考文献：
  名称：

  An Enantioselective Ketene−Imine Cycloaddition Method for Synthesis of Substituted Ring-Fused 2-Pyridinones

  摘要：

  Previously, a method for the stereoselective synthesis of P-lactams, starting from 2H-Delta (2)-thiazolines and Meldrum's acid derivatives, has been reported from our laboratory. We now report a new method for the synthesis of optically active, highly substituted ring-fused 2-pyridinones. This was discovered when 2-alkyl-Delta (2)-thiazolines and Meldrum's acid derivatives were treated with HCl(g) in benzene at 5 --> 78 degreesC. Further refinement of the synthetic protocol revealed that use of 1,2-dichloroethane as solvent at 0 --> 64 degreesC led to the desired 2-pyridinones;in good yields and with excellent enantioselectivity. Use of these conditions allowed preparation of 2-pyridinones from several different Delta (2)-thiazolines and Meldrum's acid derivatives and may be a general route to 2-pyridinones.

  DOI：

  10.1021/jo015794u

文献信息

• Synthesis and evaluation of dihydroimidazolo and dihydrooxazolo ring-fused 2-pyridones—targeting pilus biogenesis in uropathogenic bacteria
  作者：Nils Pemberton、Jerome S. Pinkner、Sofie Edvinsson、Scott J. Hultgren、Fredrik Almqvist

  DOI：10.1016/j.tet.2008.07.015

  日期：2008.9

  imidazolines were reacted with an acyl-Meldrum's acid derivative under acidic conditions. To prepare the oxygen analogs, a one-pot procedure was developed that allowed synthesis of dihydrooxazolo ring-fused 2-pyridones starting from acylated serine derivatives. After hydrolysis to their corresponding carboxylic acids and lithium carboxylates, biological evaluation revealed that the sulfur could be replaced

  先前已证明二氢噻唑环稠合的2-吡啶酮可抑制尿路致病性大肠杆菌中的菌毛组装。现在已经开发出合成二氢咪唑啉和二氢恶唑环稠合的2-吡啶酮的方法。为了获得氮类似物，使Cbz保护的咪唑啉在酸性条件下与酰基-梅德鲁姆酸衍生物反应。为了制备氧类似物，开发了一种一锅法，该程序允许从酰化的丝氨酸衍生物开始合成二氢恶唑啉环稠合的2-吡啶酮。水解成相应的羧酸和羧酸锂后，生物学评估表明硫可以被氧原子取代，并且仍然保持抑制尿路致病性大肠杆菌中菌毛组装的能力。。然而，引入仲胺而不是氧气导致生物活性大大降低。
• Microwave-assisted decarboxylation of bicyclic 2-pyridone scaffolds and identification of Aβ-peptide aggregation inhibitors
  作者：Veronica Åberg、Fredrik Norman、Erik Chorell、Andreas Westermark、Anders Olofsson、A. Elisabeth Sauer-Eriksson、Fredrik Almqvist

  DOI：10.1039/b503294f

  日期：——

  A reagent-free microwave-assisted decarboxylation procedure for carboxylic acid functionalized bicyclic 2-pyridones has been developed. This new method, based on microwave heating at 220 °C for 600 seconds in N-methyl pyrrolidone (NMP), proved to be practical and very efficient, resulting in decarboxylated 2-pyridones in near-quantitative yields. The decarboxylated products and the intermediate 2-pyridones in the form of carboxylic acid methyl esters and carboxylic acids were screened for their effect on Aβ-peptide aggregation. Two out of the 21 2-pyridones described in this study inhibited amyloid formation of the Alzheimer Aβ(1–40) peptide. The effect was seen even at a 4 : 1 ratio of 2-pyridone and monomeric Aβ-peptide.

  开发了一种无试剂的微波辅助去羧化程序，用于羧酸功能化的双环2-吡啶酮。该新方法基于在N-甲基吡咯烷酮（NMP）中以220°C加热600秒，证明实用且非常高效，产生的去羧化2-吡啶酮几乎定量。去羧化产品和羧酸甲酯及羧酸形式的中间体2-吡啶酮被筛选以研究其对Aβ肽聚集的影响。在本研究中描述的21种2-吡啶酮中，有两种抑制了阿尔茨海默病Aβ(1–40)肽的淀粉样蛋白形成。即使在2-吡啶酮与单体Aβ肽的比率为4:1时，仍观察到了这种效果。
• Structure-Based Design of Inhibitors Targeting PrfA, the Master Virulence Regulator of <i>Listeria monocytogenes</i>
  作者：Martina Kulén、Marie Lindgren、Sabine Hansen、Andrew G. Cairns、Christin Grundström、Afshan Begum、Ingeborg van der Lingen、Kristoffer Brännström、Michael Hall、Uwe H. Sauer、Jörgen Johansson、A. Elisabeth Sauer-Eriksson、Fredrik Almqvist

  DOI：10.1021/acs.jmedchem.8b00289

  日期：2018.5.10

  extensive hydrophobic network that restricts the protein’s ability to form functional DNA-binding helix–turn–helix (HTH) motifs. Our studies also revealed a hitherto unsuspected structural plasticity of the HTH motif. In conclusion, we have designed 2-pyridone analogues that function as site-AI selective PrfA inhibitors with potent antivirulence properties.

  单核细胞增生李斯特菌是一种细菌病原体，可通过转录调节剂PrfA控制其大部分毒力。在这项研究中，我们描述了结构指导的设计和一组基于环稠合的2-吡啶酮杂环的PrfA抑制剂的合成。与以前鉴定的化合物相比，我们最有效的化合物降低了毒力因子的表达，减少了细菌对真核细胞的摄取，并提高了感染单核细胞增生李斯特菌的鸡胚的存活率。晶体结构确定蛋白内“隧道”为主要抑制剂结合位点（A I），这些化合物会参与一个广泛的疏水网络，从而限制了蛋白质形成功能性DNA结合螺旋-转-螺旋（HTH）基序的能力。我们的研究还揭示了HTH母题迄今未曾想到的结构可塑性。总之，我们设计了2-吡啶酮类似物，其具有有效的抗病毒特性，可作为位点A I选择性PrfA抑制剂。
• Synthesis of Multiring Fused 2-Pyridones via a Nitrene Insertion Reaction: Fluorescent Modulators of α-Synuclein Amyloid Formation
  作者：Pardeep Singh、Erik Chorell、K. Syam Krishnan、Tomas Kindahl、Jörgen Åden、Pernilla Wittung-Stafshede、Fredrik Almqvist

  DOI：10.1021/acs.orglett.5b03190

  日期：2015.12.18

  catalyst-free, microwave-assisted, intramolecular C–H amination reaction is reported. All the synthesized polyheterocycles were evaluated for their fluorescent properties and effect on α-synuclein amyloid formation.

  据报道，一种高效，直接的方法可通过无催化剂，微波辅助的分子内C–H胺化反应合成噻唑-2-吡啶酮嵌入的拟肽多杂环化合物。评价所有合成的多杂环化合物的荧光性质以及对α-突触核蛋白淀粉样蛋白形成的影响。
• [EN] 2,3-DIHYDRO-THIAZOLO[3,2-A]PYRIDIN-5-ONE DERIVATIVES, INTERMEDIATES THEREOF, AND THEIR USE AS ANTIBACERIAL AGENTS<br/>[FR] DÉRIVÉS DE 2,3-DIHYDRO-THIAZOLO [3,2-A] PYRIDIN-5-ONE, LEURS INTERMÉDIAIRES ET LEUR UTILISATION COMME AGENTS ANTIBACTÉRIENS
  申请人：QURETECH BIO AB

  公开号：WO2016075296A1

  公开（公告）日：2016-05-19

  The disclosure relates to certain novel substituted ring-fused thiazolino 2- pyridones of Formula I, to processes for preparing such compounds, to their use in treating a bacterial infection such as a Chlamydia infection, to methods for their therapeutic use and to pharmaceutical compositions containing them.

  该披露涉及某些新型取代环融合噻唑烷基吡啶酮化合物，其化学式为I，涉及制备这类化合物的过程，以及它们在治疗细菌感染，如沙眼衣原体感染中的用途，涉及它们的治疗用途方法以及含有它们的药物组合物。