α-methylene-β,γ-diphenyl-γ-butyrolactone

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: α-methylene-β,γ-diphenyl-γ-butyrolactone
• 英文别名: 4-phenyl-3-phenyl-2-methylenebutyrolactone；3-Methylidene-4,5-diphenyloxolan-2-one
• 化学式: C₁₇H₁₄O₂
• 分子量: 250.297
• InChiKey: VLJQNNIXUWORNH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  顺式-二苯乙烯 在 吡啶 、 chromium(VI) oxide 、 sodium tetrahydroborate 、 N-溴代丁二酰亚胺(NBS) 作用下， 以 四氯化碳 、 sodium hydroxide 、 乙醇 、 二氯甲烷 为溶剂， 反应 6.0h， 生成 α-methylene-β,γ-diphenyl-γ-butyrolactone
  参考文献：
  名称：

  Synthesis of α-methylene-β,γ-diphenyl-γ-butyrolactone using cobaloxime-catalysed radical cyclisation

  摘要：

  alpha-Methylene-beta,gamma-diphenyl-gamma-butyrolactone was synthesised by the bromoprop-2-yn-1-yloxylation of stilbene 1. Cobaloxime-catalysed radical cyclisation of the resulting 1-bromo-1,2-diphenylethylprop-2-yn-1-yl ether 2 gave 2,3-diphenyl-4-methylene-tetrahydrofuran 3; oxidation of the latter with chromium trioxide in the presence of pyridine afforded target product 4 in a total yield of 25%.

  DOI：

  10.1070/mc2006v016n01abeh002082

文献信息

• 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。
• Synthesis of 3,4-disubstituted α-methylene-γ-lactones via sonochemical Barbier-type reaction
  作者：Adam Shih-Yuan Lee、Yu-Ting Chang、Shu-Huei Wang、Shu-Fang Chu

  DOI：10.1016/s0040-4039(02)02088-9

  日期：2002.11

  Barbier-type reaction condition and then followed by the in situ intramolecular esterification. The α-methylene-γ-lactone was produced as the sole product when THF/PhH solvent mixture was used whereas the allylation adduct was generated as the major product when solvent DMF was used.

  通过声化学Barbier型反应条件，通过烯丙基溴与醛的加成反应，然后原位分子内酯化，合成了一系列3,4-二取代的α-亚甲基-γ-内酯。当使用THF / PhH溶剂混合物时，α-亚甲基-γ-内酯是唯一的产物，而当使用溶剂DMF时，烯丙基化加合物是主要产物。
• Factors influencing the cytotoxicity of α-methylene-γ-hydroxy esters against pancreatic cancer
  作者：P. Veeraraghavan Ramachandran、Matthew A. Helppi、Arlie L. Lehmkuhler、Jennifer M. Marchi、C. Max Schmidt、Michele T. Yip-Schneider

  DOI：10.1016/j.bmcl.2015.07.087

  日期：2015.10

  A systematic study to identify the factors influencing the cytotoxicity of a-methylene-c-hydroxy esters against three pancreatic cancer cell lines (Panc-1, MIA-PaCa-2, and BxPC-3) has established that, in addition to Michael acceptor abilities, the possibility to lactonize to alpha-methylene-gamma-butyrolactones is as important. The substitution pattern and the number of carbons between the hydroxy and ester moieties also influence the bio-activity. (C) 2015 Elsevier Ltd. All rights reserved.
• 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.
• LAMBERT, FRANCOIS;KIRSCHLEGER, BERNARD;VILLIERAS, JEAN, J. ORGANOMET. CHEM., 406,(1991) N-2, C. 71-86
  作者：LAMBERT, FRANCOIS、KIRSCHLEGER, BERNARD、VILLIERAS, JEAN

  DOI：——

  日期：——