4-(4-hydroxy-3-methoxyphenyl)-2-methylenebutyrolactone | 1447662-19-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 4-(4-hydroxy-3-methoxyphenyl)-2-methylenebutyrolactone
• 英文别名: 5-(4-hydroxy-3-methoxyphenyl)-3-methylenedihydrofuran-2(3H)-one；5-(4-Hydroxy-3-methoxyphenyl)-3-methylideneoxolan-2-one；5-(4-hydroxy-3-methoxyphenyl)-3-methylideneoxolan-2-one
• CAS: 1447662-19-2
• 化学式: C₁₂H₁₂O₄
• 分子量: 220.225
• InChiKey: CPMUMFAQGCARMD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(4-hydroxy-3-methoxyphenyl)-2-methylenebutyrolactone 、 邻氟氯苄 在 potassium carbonate 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以62%的产率得到
  参考文献：
  名称：

  发现含有香草醛部分的新型 α-亚甲基-γ-丁内酯衍生物作为抗病毒和抗真菌剂

  摘要：

  在烟内酯A（L1）结构的基础上，通过结构简化和活性片段置换策略，设计合成了一系列新型α-亚甲基-γ-丁内酯衍生物B1-B43，并对其抗病毒和抗真菌活性进行了评价。生物测定研究表明，许多目标化合物对烟草花叶病毒 (TMV) 具有良好至优异的抗病毒活性，其中一些化合物对Valsa mali和Fusarium graminearum表现出特定的抗真菌活性。化合物B32在体内表现出最好的抗TMV活性（灭活效果，88.9%；保护效果，65.8%；疗效，52.8%）500 mg/L，明显高于市售杀病毒剂利巴韦林和宁南霉素。化合物B32的抑制作用也通过使用绿色荧光蛋白 (GFP) 标记的 TMV 的接种试验显现。研究了化合物B32的初步抗病毒机制。透射电子显微镜 (TEM) 显示化合物B32可以破坏病毒颗粒的完整性。然后，分子对接和等温滴定量热法 (ITC) 分析进一步证明，化合物B32对 TMV 外壳蛋白表现出很强的结合亲和力，其解离常数

  DOI：

  10.1021/acs.jafc.2c03632
• 作为产物：
  描述：

  在 盐酸 作用下， 以 水 为溶剂， 生成 4-(4-hydroxy-3-methoxyphenyl)-2-methylenebutyrolactone
  参考文献：
  名称：

  New antifungal scaffold derived from a natural pharmacophore: Synthesis of α-methylene-γ-butyrolactone derivatives and their antifungal activity against Colletotrichum lagenarium

  摘要：

  Thirty new and thirty-four known analogues were designed and synthesized to improve the potential use of the alpha-methylene-gamma-butyrolactone ring, a natural pharmacophore. All structures were confirmed by H-1 and C-13 NMR, MS, and single-crystal X-ray diffraction analyses. The results of antifungal and cytotoxic activity indicated that the synthesized analogues showed significant inhibitory activity and limited selectivity. Compound 45 exhibited the highest antifungal activity with IC50 = 22.8 mu M but moderate cytotoxic activity with IC50 = 28.5 mu M (against BGC823 cell line) and 7.7 mu M (against HeLa cell line). Analysis of structure-activity relationships revealed that the incorporation of an aromatic ring into the beta, gamma positions of the lactone ring improved antifungal activity, and that the introduction of electron-withdrawing groups into the aromatic rings increased the activity compared with electron-donating groups. The above results identified 4-phenyl-3-phenyl-2-methylenebutyrolactone (33) as a lead scaffold for discovering and developing novel and improved crop-protection agents. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.05.073

文献信息

• 含α-亚甲基-γ-丁内酯结构的酚类衍生物、制备方法及其应用
  申请人：西北农林科技大学

  公开号：CN113968833B

  公开（公告）日：2023-02-28

  本发明公开了一种含α‑亚甲基‑γ‑丁内酯结构的酚类衍生物、制备方法及其应用。本发明依据活性拼接原理，合成了一系列结构新颖的含α‑亚甲基‑γ‑丁内酯酚类衍生物；同时开发了两条合成路线，并对反应条件进行了优化，得到最佳反应条件，合成方法步骤短，原料易得，收率高；并对其使用半叶枯斑法测试了含α‑亚甲基‑γ‑丁内酯酚类衍生物对烟草花叶病毒(TMV)病的抑制率，结果表明，该类化合物表现出了优异的抗植物病毒活性，在100～500ppm施药量的情况下，对烟草花叶病毒呈现钝化活性、治疗活性和保护活性。
• New antifungal scaffold derived from a natural pharmacophore: Synthesis of α-methylene-γ-butyrolactone derivatives and their antifungal activity against Colletotrichum lagenarium
  作者：Feng Jun-Tao、Wang De-Long、Wu Yong-Ling、Yan He、Zhang Xing

  DOI：10.1016/j.bmcl.2013.05.073

  日期：2013.8

  Thirty new and thirty-four known analogues were designed and synthesized to improve the potential use of the alpha-methylene-gamma-butyrolactone ring, a natural pharmacophore. All structures were confirmed by H-1 and C-13 NMR, MS, and single-crystal X-ray diffraction analyses. The results of antifungal and cytotoxic activity indicated that the synthesized analogues showed significant inhibitory activity and limited selectivity. Compound 45 exhibited the highest antifungal activity with IC50 = 22.8 mu M but moderate cytotoxic activity with IC50 = 28.5 mu M (against BGC823 cell line) and 7.7 mu M (against HeLa cell line). Analysis of structure-activity relationships revealed that the incorporation of an aromatic ring into the beta, gamma positions of the lactone ring improved antifungal activity, and that the introduction of electron-withdrawing groups into the aromatic rings increased the activity compared with electron-donating groups. The above results identified 4-phenyl-3-phenyl-2-methylenebutyrolactone (33) as a lead scaffold for discovering and developing novel and improved crop-protection agents. (C) 2013 Elsevier Ltd. All rights reserved.
• Discovery of Novel α-Methylene-γ-Butyrolactone Derivatives Containing Vanillin Moieties as Antiviral and Antifungal Agents
  作者：Hong-Wei He、Fei-Yu Wang、Danyang Zhang、Cai-Yun Chen、Dan Xu、Huan Zhou、Xili Liu、Gong Xu

  DOI：10.1021/acs.jafc.2c03632

  日期：2022.8.24

  α-methylene-γ-butyrolactone derivatives B1–B43 were designed and synthesized by structure simplification and active fragment replacement strategies, and their antiviral and antifungal activities were evaluated. The bioassay studies indicated that many target compounds possessed good to excellent antiviral activity against tobacco mosaic virus (TMV) and some of these compounds exhibited specific antifungal activities

  在烟内酯A（L1）结构的基础上，通过结构简化和活性片段置换策略，设计合成了一系列新型α-亚甲基-γ-丁内酯衍生物B1-B43，并对其抗病毒和抗真菌活性进行了评价。生物测定研究表明，许多目标化合物对烟草花叶病毒 (TMV) 具有良好至优异的抗病毒活性，其中一些化合物对Valsa mali和Fusarium graminearum表现出特定的抗真菌活性。化合物B32在体内表现出最好的抗TMV活性（灭活效果，88.9%；保护效果，65.8%；疗效，52.8%）500 mg/L，明显高于市售杀病毒剂利巴韦林和宁南霉素。化合物B32的抑制作用也通过使用绿色荧光蛋白 (GFP) 标记的 TMV 的接种试验显现。研究了化合物B32的初步抗病毒机制。透射电子显微镜 (TEM) 显示化合物B32可以破坏病毒颗粒的完整性。然后，分子对接和等温滴定量热法 (ITC) 分析进一步证明，化合物B32对 TMV 外壳蛋白表现出很强的结合亲和力，其解离常数