4-(3-methoxyphenyl)-2-methylenebutyrolactone | 192457-46-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-(3-methoxyphenyl)-2-methylenebutyrolactone
• 英文别名: 5-(3-methoxyphenyl)-3-methylenedihydrofuran-2(3H)-one；Dihydro-5-(3-methoxyphenyl)-3-methylene-2(3H)-furanone；5-(3-methoxyphenyl)-3-methylideneoxolan-2-one
• CAS: 192457-46-8
• 化学式: C₁₂H₁₂O₃
• 分子量: 204.225
• InChiKey: GWILNBKRICTGMP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  15
• 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：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(3-methoxyphenyl)-2-methylenebutyrolactone 在 tris-(dipivaloylmethanato)manganese(III) 、 苯硅烷 、 氧气 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 以26 %的产率得到(±)-3-hydroxy-5-(3-methoxyphenyl)-3-methyldihydrofuran-2(3H)-one
  参考文献：
  名称：

  烟内酯类似物抗 TMV 的合成及构效关系研究

  摘要：

  最初提出的 (±)-烟内酯 A 结构的合成是一种具有三个连续手性中心的强效抗病毒木脂素，从丙烯酸甲酯开始分 5 步合成。合成的关键步骤包括 In 催化的区域选择性烯丙基化和 Mn 催化的 Mukaiyama 水合反应。我们的合成策略还使我们能够获得其他三种差向异构体并研究构效关系。合成化合物的核磁共振数据与分离样品的核磁共振数据不匹配，表明烟内酯 A 的结构仍有待重新分配。评估了所有合成目标化合物的抗烟草花叶病毒 (anti-TMV) 活性。生物测定结果表明，(±)-8-去甲基烟内酯 A 显示出与市售药物宁南霉素相似的抗 TMV 活性，

  DOI：

  10.1055/a-1814-9637
• 作为产物：
  描述：

  在 盐酸 作用下， 以 水 为溶剂， 生成 4-(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

• Isatin Derived Spirocyclic Analogues with α-Methylene-γ-butyrolactone as Anticancer Agents: A Structure–Activity Relationship Study
  作者：Sandeep Rana、Elizabeth C. Blowers、Calvin Tebbe、Jacob I. Contreras、Prakash Radhakrishnan、Smitha Kizhake、Tian Zhou、Rajkumar N. Rajule、Jamie L. Arnst、Adnan R. Munkarah、Ramandeep Rattan、Amarnath Natarajan

  DOI：10.1021/acs.jmedchem.6b00400

  日期：2016.5.26

  Design, synthesis, and evaluation of α-methylene-γ-butyrolactone analogues and their evaluation as anticancer agents is described. SAR identified a spirocyclic analogue 19 that inhibited TNFα-induced NF-κB activity, cancer cell growth and tumor growth in an ovarian cancer model. A second iteration of synthesis and screening identified 29 which inhibited cancer cell growth with low-μM potency. Our data

  描述了α-亚甲基-γ-丁内酯类似物的设计，合成和评估及其作为抗癌剂的评估。SAR鉴定出在卵巢癌模型中可抑制TNFα诱导的NF-κB活性，癌细胞生长和肿瘤生长的螺环类似物19。合成和筛选的第二次迭代确定了29个以低μM效能抑制癌细胞生长的物质。我们的数据表明，从伊斯兰衍生的螺环α-亚甲基-γ-丁内酯是用于优化识别新型抗癌药的合适核心。
• Enantioselective Dreiding-Schmidt reactions: asymmetric synthesis and analysis of α-methylene-γ-butyrolactones
  作者：René Csuk、Christina Schröder、Sonja Hutter、Kristina Mohr

  DOI：10.1016/s0957-4166(97)00166-3

  日期：1997.5

  The zinc/silver-graphite mediated Dreiding-Schmidt reactions between aldehydes and the 2-bromomethyl-acrylate derived sultamamides (+)/(-)-28 or (+)/(-)-30 gave the corresponding substituted alpha-methylene-gamma-butyrolactones with ee's up to 90%. Enantiomerically pure compounds were obtained by semipreparative HPLC using a chiral stationary phase. (C) 1997 Elsevier Science Ltd.
• 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.
• Synthesis and Structure–Activity Relationship Studies of Nicot­lactone Analogues as Anti-TMV Agents
  作者：Huan Zhou、Gong Xu、Hong-Wei He、Yuan Chi、Cai-Yun Chen、Fei-Yu Wang、Jia-Xin Wang、Dan Xu

  DOI：10.1055/a-1814-9637

  日期：2022.8

  the structure–activity relationship. The NMR data of the synthesized compounds do not match that of the isolated sample, indicating that the structure of nicotlactone A remains to be reassigned. All the synthetic target compounds were evaluated for their anti-tobacco mosaic virus (anti-TMV) activity. Bioassay results indicated that (±)-8-demethylnicotlactone A displayed similar anti-TMV activity to

  最初提出的 (±)-烟内酯 A 结构的合成是一种具有三个连续手性中心的强效抗病毒木脂素，从丙烯酸甲酯开始分 5 步合成。合成的关键步骤包括 In 催化的区域选择性烯丙基化和 Mn 催化的 Mukaiyama 水合反应。我们的合成策略还使我们能够获得其他三种差向异构体并研究构效关系。合成化合物的核磁共振数据与分离样品的核磁共振数据不匹配，表明烟内酯 A 的结构仍有待重新分配。评估了所有合成目标化合物的抗烟草花叶病毒 (anti-TMV) 活性。生物测定结果表明，(±)-8-去甲基烟内酯 A 显示出与市售药物宁南霉素相似的抗 TMV 活性，