diethyl 2,6-dimethyl-4-phenyl-4H-pyran-3,5-dicarboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃
• 英文名称: diethyl 2,6-dimethyl-4-phenyl-4H-pyran-3,5-dicarboxylate
• 英文别名: 3,5-diethoxycarbonyl-2,6-dimethyl-4-phenyl-4H-pyran
• 化学式: C₁₉H₂₂O₅
• 分子量: 330.381
• InChiKey: BUTMHFPJIIMPHS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  diethyl 2,6-dimethyl-4-phenyl-4H-pyran-3,5-dicarboxylate 以 四氢呋喃 、 甲醇 为溶剂， 以35.1 %的产率得到tetraethyl 2,4,8,10-tetramethyl-6,12-bisphenyl-3,9-dioxapentacyclo[6.4.0.0^2,7.0^4,11.0^5,10]dodecane-1,5,7,11-tetracarboxylate
  参考文献：
  名称：

  洞察 4-aryl-4H-pyran 的光化学反应：实验和理论研究

  摘要：

  在本文中，我们研究了 4-aryl-4 H - pyran 的光化学反应，发现结构对称性对其光化学行为有重要影响。当使用对称的 4-aryl-4 H - pyran 时，例如 2,6-dimethyl-4-aryl-4 H -pyran-3,5-dicarboxylate 二乙酯，主要进行 [2 + 2] 光环加成反应。而不对称的 4- aryl-4 H -pyran，如 2-amino-3-cyano-4-aryl-4 H - pyran，主要进行光裂解反应。为了推测反应机理，在B3LYP-D3/def2TZVP//B3LYP-D3/6-31G(d)水平进行了密度泛函理论（DFT）和时间相关密度泛函理论（TDDFT）计算。结果表明，二乙基 2,6-二甲基-4-aryl-4H -pyran-3,5-dicarboxylate 经过两步 [2 + 2] 光环加成，通过分子间和分子内反应得到 3

  DOI：

  10.1016/j.tet.2022.133212
• 作为产物：
  描述：

  乙酰乙酸乙酯 、 苯甲醛 在 乙酸酐 、 zinc(II) chloride 作用下， 生成 diethyl 2,6-dimethyl-4-phenyl-4H-pyran-3,5-dicarboxylate
  参考文献：
  名称：

  洞察 4-aryl-4H-pyran 的光化学反应：实验和理论研究

  摘要：

  在本文中，我们研究了 4-aryl-4 H - pyran 的光化学反应，发现结构对称性对其光化学行为有重要影响。当使用对称的 4-aryl-4 H - pyran 时，例如 2,6-dimethyl-4-aryl-4 H -pyran-3,5-dicarboxylate 二乙酯，主要进行 [2 + 2] 光环加成反应。而不对称的 4- aryl-4 H -pyran，如 2-amino-3-cyano-4-aryl-4 H - pyran，主要进行光裂解反应。为了推测反应机理，在B3LYP-D3/def2TZVP//B3LYP-D3/6-31G(d)水平进行了密度泛函理论（DFT）和时间相关密度泛函理论（TDDFT）计算。结果表明，二乙基 2,6-二甲基-4-aryl-4H -pyran-3,5-dicarboxylate 经过两步 [2 + 2] 光环加成，通过分子间和分子内反应得到 3

  DOI：

  10.1016/j.tet.2022.133212

文献信息

• NbCl5-promoted the synthesis of 4H-pyrans through multicomponent reaction
  作者：Mayara de Souza Siqueira、Luiz Carlos da Silva-Filho

  DOI：10.1016/j.tetlet.2016.10.008

  日期：2016.11

  Multicomponent reactions between β-ketoesters and benzaldehydes for the synthesis of 4H-pyran derivatives promoted by niobium pentachloride (NbCl5) were carried out, providing good yields and reasonable reaction times under mild reaction conditions.

  进行了β-酮酸酯和苯甲醛之间的多组分反应，以合成由五氯化铌（NbCl 5）促进的4 H-吡喃衍生物，在温和的反应条件下提供了良好的收率和合理的反应时间。
• Optimization of the Selective Monohydrolysis of Diethyl 4-Aryl-4H-pyran-3,5-dicarboxylates
  作者：Jiaojiao Duan、Xiaohui Song、Hong Yan、Xiuqing Song

  DOI：10.3390/molecules16053845

  日期：——

  A simple, efficient and eco-friendly procedure for the selective monohydrolysis of diethyl 2,6-dimethyl-4-aryl-4H-pyran-3,5-dicarboxylates under quaternary ammonium salt catalysis conditions is presented. The catalytic activities of various quaternary ammonium salts were investigated using different molar ratios of NaOH and water-organic solvent mixtures. The results indicate that the combination of 1.0 equivalent of tetraethyl-ammonium bromide (TEAB) with 1.2 equivalents of NaOH in a 10% water-ethanol media at 40 °C displays remarkable selectivity for the monohydrolysis of diethyl 2,6-dimethyl-4-aryl-4H-pyran-3,5-dicarboxylates. The utility of this process is demonstrated by the monohydrolysis of a series of 4-aryl-4H-pyran-3,5-dicarboxylate esters to afford the corresponding monoesters in 20–80% yields under the optimized conditions.

  本研究介绍了一种在季铵盐催化条件下选择性单水解 2,6-二甲基-4-芳基-4H-吡喃-3,5-二甲酸二乙酯的简单、高效且环保的方法。使用不同摩尔比的 NaOH 和水-有机溶剂混合物研究了各种季铵盐的催化活性。结果表明，在 10%的水-乙醇介质中，温度为 40 °C，将 1.0 等量的四乙基溴化铵 (TEAB) 与 1.2 等量的 NaOH 混合使用，对 2,6-二甲基-4-芳基-4H-吡喃-3,5-二甲酸二乙酯的单水解具有显著的选择性。在优化的条件下，一系列 4-芳基-4H-吡喃-3,5-二羧酸酯的单水解反应得到了相应的单酯，产率达到 20-80%，证明了该工艺的实用性。
• Synthesis and Biological Evaluation of 3,9-Dioxatetraasteranes as <i>C</i><sub>2</sub>-Symmetric HIV-1 Protease Inhibitors and Docking Study
  作者：Peng Li、Shijie Wang、Huiqin Wang、Hong Yan

  DOI：10.1248/bpb.b18-00705

  日期：2019.2.1

  A series of tetraethyl 2,4,8,10-tetramethyl-6,12-diaryl-3,9-dioxahexacyclo[6.4.0.02,7.04,11.05,10]dodecane-1,5,7,11-tetracarboxylates (simplified as 3,9-dioxatetraasteranes) with C2-symmetric structural characteristics were synthesized through the [2 + 2] photocycloaddition of the diethyl 2,6-dimethyl-4-aryl-4H-pyran-3,5-dicarboxylates. Besides, their anti-human immunodeficiency virus (HIV)-1 activities were evaluated by enzyme-linked immunosorbent assay (ELISA) assay against HIV-1 (IIIB) replication in MT-4 cell culture. The result showed that the tested compounds exhibited potential activates with IC50 values less than 110 nM. Furthermore, docking study was carried out to study the binding mode of these compounds. The results indicated that the overall orientation of the inhibitors in the active site were similar to that of the cyclic urea AHA001 and a hydrogen bond with the protein residues might play a crucial role in their anti-HIV-1 activities. Such results will provide a theoretical foundation for further investigations on the biological activity of 3,9-dioxatetraasteranes.

  一系列具有 C2 对称结构特征的 2,4,8,10-四甲基-6,12-二芳基-3,9-二氧杂六环[6.4.0.02,7.04,11.通过 2,6-二甲基-4-芳基-4H-吡喃-3,5-二甲酸二乙酯的[2 + 2]光环加成反应，合成了具有 C2 对称结构特征的十二烷-1,5,7,11-四羧酸盐（简化为 3,9-二氧杂四烷烃）。此外，还通过酶联免疫吸附试验（ELISA）评估了这些化合物在 MT-4 细胞培养中对 HIV-1 (IIIB) 复制的抗人类免疫缺陷病毒（HIV）-1 活性。结果表明，受试化合物具有潜在的活性，其 IC50 值小于 110 nM。此外，还对这些化合物的结合模式进行了对接研究。结果表明，抑制剂在活性位点的整体取向与环状脲 AHA001 相似，与蛋白质残基的氢键可能在它们的抗 HIV-1 活性中起着关键作用。这些结果将为进一步研究 3,9-二氧四酰胺类化合物的生物活性提供理论基础。
• Synthesis and Biological Evaluation of 3,9-Dioxatetraasteranes as Potential Inhibitors of Epidermal Growth Factor Receptor
  作者：Hong Yan、Hongjun Wang、Nana Tian、Dongchen Chu

  DOI：10.2174/1570180819666220928151144

  日期：2022.9.28

  Epidermal growth factor receptor (EGFR) is a validated and therapeutically amenable target, and inhibition of the EGFR signaling pathway has emerged as an attractive target for cancer therapy.

  The present work was designed to synthesize and evaluate the antiproliferative activity activity of a novel series of 3,9-dioxatetraasteranes as potential inhibitors of EGFR. All target compounds were evaluated for antiproliferative activity in vitro against A549 and HepG2 cell lines.

  Among the target compounds, compound B13 displayed the most potent antiproliferative activity against A549 with IC50 = 4.31 μM and HepG2 with IC50 = 6.92 μM. In addition, a molecular docking study was performed to investigate the binding mode and binding capacity with EGFR (PDB code: 1M17).

  The results indicated that 3,9-dioxatetraasteranes may be promising potential EGFR inhibitors.

  背景： 表皮生长因子受体（表皮生长因子受体，EGFR）是一个已被证实且可用于治疗的靶点，抑制表皮生长因子受体信号通路已成为癌症治疗的一个有吸引力的靶点。 方法： 本研究旨在合成和评估一系列新型 3,9-二氧四酰胺类化合物作为表皮生长因子受体潜在抑制剂的抗增殖活性。所有目标化合物都针对 A549 和 HepG2 细胞系进行了体外抗增殖活性评估。 结果显示 在目标化合物中，化合物 B13 对 A549 的抗增殖活性最强（IC50 = 4.31 μM），对 HepG2 的抗增殖活性最强（IC50 = 6.92 μM）。此外，还进行了分子对接研究，以探讨与表皮生长因子受体（PDB 代码：1M17）的结合模式和结合能力。 结果表明 研究结果表明，3,9-二氧四酰胺类化合物可能是很有潜力的表皮生长因子受体抑制剂。
• SnCl2/nano SiO2: A green and reusable heterogeneous catalyst for the synthesis of polyfunctionalized 4H-pyrans
  作者：Javad Safaei-Ghomi、Raheleh Teymuri、Hossein Shahbazi-Alavi、Abolfazl Ziarati

  DOI：10.1016/j.cclet.2013.06.021

  日期：2013.10

  A highly efficient and general method for the synthesis of polyfunctionalized 4H-pyrans is established through a one-pot multicomponent cyclocondensation of aromatic aldehydes with CH acids, malononitrile and ethyl acetoacetate using nano silica supported tin (II) chloride as a catalyst. In this method SnCl2/nano SiO2 was used as green and reusable catalyst. Excellent yields, short reaction times, simple workup, and inexpensiveness and commercially availability of the catalyst are the advantages of this method. (C) 2013 Javad Safaei-Ghomi. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.