5-(4-fluorophenyl)-3-methylenedihydrofuran-2(3H)-one | 147596-64-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-(4-fluorophenyl)-3-methylenedihydrofuran-2(3H)-one
• 英文别名: 5-(4-Fluorophenyl)-3-methylideneoxolan-2-one
• CAS: 147596-64-3
• 化学式: C₁₁H₉FO₂
• 分子量: 192.19
• InChiKey: IEFYWLKUIUAKDJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(4-氟苯甲酰基)哌啶 、 5-(4-fluorophenyl)-3-methylenedihydrofuran-2(3H)-one 在 溶剂黄146 作用下， 以 乙醚 、 乙醇 为溶剂， 反应 24.0h， 以53%的产率得到3-<4-(4-fluorobenzoyl)piperidinomethyl>-5-(4-fluorophenyl)-4,5-dihydro-2(3H)-furanon
  参考文献：
  名称：

  内酯，XXY：一些氟代苯基化的α-氨基甲基内酯的合成和5-HT2-受体亲和力。

  摘要：

  DOI：

  10.1002/ardp.19933260413
• 作为产物：
  描述：

  cis/trans-5-(4-Fluorphenyl)-2-oxo-4,5-dihydro-3H-furan-3-carbonsaeure 在 聚合甲醛 、 sodium acetate 、 二乙胺 作用下， 以 溶剂黄146 为溶剂， 以42%的产率得到5-(4-fluorophenyl)-3-methylenedihydrofuran-2(3H)-one
  参考文献：
  名称：

  内酯，第 23 版：丁酰苯型“γ-内酯化”精神安定药的合成和立体化学

  摘要：

  “Γ-内酯化”︁ 精神安定剂 (1,2a-c) 可以从 α-甲酰基、α-羧基-和 α-亚甲基内酯 5-7a、b 通过与胺 8a-c 反应获得。6a和1a-c以顺式/反式混合物为主，主要为顺式，6b和2a为顺式/反式混合物，主要为反式。2b、c 分离出纯反式异构体。

  DOI：

  10.1002/ardp.19933260111

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。
• Fluorous tagging: an enabling isolation technique for indium-mediated allylation reactions in water
  作者：Carolyn S. Reid、Yuhua Zhang、Chao-Jun Li

  DOI：10.1039/b713244c

  日期：——

  An efficient method was developed to allylate aldehydes using an aqueous indium-mediated allylation reaction with fluorous-tagged allyl halides, and to directly purify the products by fluorous solid phase extraction (F-SPE).

  开发了一种高效的方法，通过使用含氟标记的烯丙基卤化物进行水相铟介导的烯丙基化反应来烯丙基化醛，并通过含氟固相萃取（F-SPE）直接纯化产物。
• Synthesis of (<i>E</i>)- and (<i>Z</i>)-α-Alkylidene-γ-aryl-γ-butyrolactones via Alkenylalumination of Oxiranes
  作者：P. Veeraraghavan Ramachandran、Garrett Garner、Debarshi Pratihar

  DOI：10.1021/ol702079f

  日期：2007.11.1

  presence of BF(3).Et(2)O, affords the corresponding (Z)-alpha-alkylidene-gamma-aryl-gamma-hydroxy esters in 81-100% Z-selectivity. Chromatographic separation of isomers, followed by lactonization with trifluoroacetic acid, provides isomerically pure (Z)-alpha-alkylidene-gamma-aryl-gamma-butyrolactones in 53-78% overall yield. Isomerization of the (Z)-alkylidene hydroxyl esters using LDA, followed by

  在BF（3）.Et（2）O存在下，用[α-（乙氧基羰基）链烯基]二异丁基铝对取代的苯乙烯氧化物进行烯基铝化，得到相应的（Z）-α-亚烷基-γ-芳基-γ-羟基酯Z选择性达到81-100％。色谱分离异构体，然后用三氟乙酸内酯化，以53-78％的总收率提供异构纯的（Z）-α-亚烷基-γ-芳基-γ-丁内酯。使用LDA对（Z）-亚烷基羟基酯进行异构化，然后使用庞大的质子源（例如BHT）进行质子化，提供了一条简单的途径，可以将相应的α-（E）-亚烷基-γ-苯基-γ-羟基酯产率为72-78％，将其环化以得到产率为78-85％的相应的（E）-丁内酯。
• 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.
• An Improved Procedure for α-Methylenation of Lactones
  作者：Maria M. Murta、Mariangela B. M. de Azevedo、Andrew E. Greene

  DOI：10.1080/00397919308009804

  日期：1993.2

  A variety of gamma-butyrolactones, as well as a delta-valerolactone and an ester, have been efficiently converted to their alpha-methylene derivatives by using an improved decarboxylative methylenation procedure, which is simpler and more general than the previously described method.