(Z)-1,2-difluoro-1-(3,4,5-trimethoxyphenyl)-2-(3-hydroxy-4-methoxyphenyl) ethene

• 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: (Z)-1,2-difluoro-1-(3,4,5-trimethoxyphenyl)-2-(3-hydroxy-4-methoxyphenyl) ethene
• 英文别名: 5-[(Z)-1,2-difluoro-2-(3,4,5-trimethoxyphenyl)ethenyl]-2-methoxyphenol
• 化学式: C₁₈H₁₈F₂O₅
• 分子量: 352.335
• InChiKey: NKLVCDSGWUCIPR-MSUUIHNZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  57.2
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (Z)-1,2-difluoro-1-(3,4,5-trimethoxyphenyl)-2-(3-hydroxy-4-methoxyphenyl) ethene 、 亚磷酸二苄酯 在 四氯化碳 、 N,N-二异丙基乙胺 、 三甲基氯硅烷 、 sodium bromide 、 sodium hydroxide 、 水 作用下， 以 乙腈 为溶剂， 反应 17.0h， 生成 (Z)-1,2-difluoro-1-(3,4,5-trimethoxyphenyl)-2-(3-hydroxy-4-methoxyphenyl)ethene O-disodium phosphate
  参考文献：
  名称：

  Synthesis and Biological Activity of Fluorinated Combretastatin Analogues

  摘要：

  With the aim of understanding the influence of fluorine on the double bond of the cis-stilbene moiety of combretastatin derivatives and encouraged by a preliminary molecular modeling study showing a different biological environment on the interaction site with tubulin, we prepared, through various synthetic approaches, a small library of compounds in which one or both of the olefinic hydrogens were replaced with fluorine. X-ray analysis on the difluoro-CA-4 analogue demonstrated that the spatial arrangement of the molecule was not modified, compared to its nonfluorinated counterpart. SAR analysis confirmed the importance of the cis-stereochemistry of the stilbene scaffold. Nevertheless, some unpredicted results were observed on a few trans-fluorinated derivatives. The position of a fluorine atom on the double bond may affect the inhibition of tubulin polymerization and cytotoxic activity of these compounds.

  DOI：

  10.1021/jm701362m
• 作为产物：
  描述：

  (Z)-1,2-difluoro-1-(3,4,5-trimethoxyphenyl)-2-(4-methoxy-3-tert-butyl-dimethyl-silyloxyphenyl)ethene 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以83%的产率得到(Z)-1,2-difluoro-1-(3,4,5-trimethoxyphenyl)-2-(3-hydroxy-4-methoxyphenyl) ethene
  参考文献：
  名称：

  [EN] FLUOROCOMBRETASTATIN AND DERIVATIVES THEREOF
  [FR] FLUOROCOMBRETASTATINE ET SES DERIVES

  摘要：

  公开号：

  WO2005007603A3

文献信息

• Synthesis of Bromoundecyl Resorc[4]arenes and Applications of the Cone Stereoisomer as Selector for Liquid Chromatography
  作者：Silvia Corradi、Giulia Mazzoccanti、Francesca Ghirga、Deborah Quaglio、Laura Nevola、Chiara Massera、Franco Ugozzoli、Giuseppe Giannini、Alessia Ciogli、Ilaria D’Acquarica

  DOI：10.1021/acs.joc.8b00488

  日期：2018.8.3

  C-alkylated resorc[4]arenes, we planned to immobilize on a solid support resorc[4]arenes with C11-long side chains in the lower rim. To this purpose, we synthesized two conformationally diverse resorc[4]arenes containing a bromoundecyl moiety in the four axial pendants. The cone stereoisomer 6a (30% yield) was selected for the reaction with an aminopropylated silica gel (APSG) obtained from spherical Kromasil

  作为我们对C-烷基化间苯二酚[4]芳烃多面性质的研究的扩展，我们计划将其固定在下边缘具有C 11-长侧链的固相支持间苯二酚[4]芳烃上。为了这个目的，我们合成了两个构型多样的间苯二[4]芳烃，在四个轴向侧基中含有一个溴氰基部分。选择圆锥立体异构体6a（30％的产率）与从球形Kromasil Si 100、5μm颗粒获得的氨基丙基化硅胶（APSG）反应，得到相应的固定化SP-C 11 -resorc [4]芳烃体系。对生成的极性包埋的固定相进行了充分表征，并在HPLC鉴别E / Z中进行了研究。天然存在的和半合成的康维他汀的立体异构体，康维他汀是（Z）-二苯乙烯抗癌药家族。椅子立体异构体6b（收率20％）在进行X射线衍射分析时显示出在晶格中值得注意的自组装，这是由于分子间Br··O卤素键相互作用而插入的疏水层和极性层的结果，根据独特的堆叠图案。在反相（RP）条件下分离高极性天然产物（即类黄酮
• Fluorocombretastatin and derivatives thereof
  申请人：Giannini Giuseppe

  公开号：US20060160778A1

  公开（公告）日：2006-07-20

  The present invention is related to new derivatives of Combretastatin, of Formula obtained by total synthesis. The strategy developed for each of the compounds is to i) replace a halogen (i.e. fluorine atom) to hydrogen on olefinic bound; ii) replace an aromatic ring in a natural product with an amino-aromatic ring. Said compounds recognize and bind the tubulin site: are useful for treating pathological states which arise from or are exacerbated by cell proliferation—as anticancer and/or antiangiogenic activity, in a mammal—to pharmaceutical compositions comprising these compounds.

  本发明涉及通过全合成获得的Combretastatin新衍生物，其化学式为。每种化合物的策略是：i）在烯丙基键上用氢替换卤素（即氟原子）；ii）用氨基芳香环替换天然产物中的芳香环。所述化合物识别并结合微管蛋白位点：适用于治疗由细胞增殖引起或加剧的病理状态，作为哺乳动物中的抗癌和/或抗血管生成活性，以及包含这些化合物的制药组合物。
• [EN] FLUOROCOMBRETASTATIN AND DERIVATIVES THEREOF<br/>[FR] FLUOROCOMBRETASTATINE ET SES DERIVES
  申请人：SIGMA TAU IND FARMACEUTI

  公开号：WO2005007603A3

  公开（公告）日：2005-07-07
• US7572778B2
  申请人：——

  公开号：US7572778B2

  公开（公告）日：2009-08-11
• Synthesis and Biological Activity of Fluorinated Combretastatin Analogues
  作者：Domenico Alloatti、Giuseppe Giannini、Walter Cabri、Isabella Lustrati、Mauro Marzi、Andrea Ciacci、Grazia Gallo、M. Ornella Tinti、Marcella Marcellini、Teresa Riccioni、Mario B. Guglielmi、Paolo Carminati、Claudio Pisano

  DOI：10.1021/jm701362m

  日期：2008.5.1

  With the aim of understanding the influence of fluorine on the double bond of the cis-stilbene moiety of combretastatin derivatives and encouraged by a preliminary molecular modeling study showing a different biological environment on the interaction site with tubulin, we prepared, through various synthetic approaches, a small library of compounds in which one or both of the olefinic hydrogens were replaced with fluorine. X-ray analysis on the difluoro-CA-4 analogue demonstrated that the spatial arrangement of the molecule was not modified, compared to its nonfluorinated counterpart. SAR analysis confirmed the importance of the cis-stereochemistry of the stilbene scaffold. Nevertheless, some unpredicted results were observed on a few trans-fluorinated derivatives. The position of a fluorine atom on the double bond may affect the inhibition of tubulin polymerization and cytotoxic activity of these compounds.