2-ferrocenyl-chromen-4-one | 1332699-47-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 2-ferrocenyl-chromen-4-one
• 英文别名: cyclopenta-1,3-diene;2-cyclopenta-2,4-dien-1-ylchromen-4-one;iron(2+)
• CAS: 1332699-47-4
• 化学式: C₁₉H₁₄FeO₂
• 分子量: 330.166
• InChiKey: FOCCFIGBCAANQZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.58
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  oxone 、 2-ferrocenyl-chromen-4-one 以 二氯甲烷 、 水 、 丙酮 为溶剂， 以80%的产率得到3-hydroxy-2-ferrocenylchromen-4-one
  参考文献：
  名称：

  Synthesis and Structural Characterization of Ferrocenyl-Substituted Aurones, Flavones, and Flavonols

  摘要：

  In the context of our studies on the modification of bioactive molecules with ferrocene, we here report the first examples of ferrocenyl flavonoids, where ferrocene replaces the B ring of the flavonoid skeleton. Ferrocenyl aurones possessing an electron-withdrawing or an electron-donating group in the 5'-position were obtained from 5'-R-2'-hydroxy-3-ferrocenyl chalcones via 1,5 oxidative exocyclization using Hg(OAc)(2) or AgOTf. Treatment of the ferrocenyl aurones with LDA resulted in a ring opening to form ferrocenyl ynones, which could then be selectively recydized to the flavone isomer by treatment with NaOEt. Ferrocenyl flavones were also obtained by isomerization of the aurones with KCN and were hydroxylated in the 3-position to form ferrocenyl flavonols with oxone in a biphasic reaction. In many cases the reactivity of the ferrocenyl compounds was significantly different from that of their organic analogues. This reactivity and regioselectivity can be rationalized by ferrocene's particular ability to destabilize alpha-anions in reaction intermediates. Representative examples of ferrocenyl aurones, ynones, and flavones were characterized by 2D NMR and X-ray crystallography, and the molecules all show a planar arrangement of the organic skeleton with the cyclopentadienyl ring of the ferrocene group. Putative MLCT bands in the visible region are responsible for the variety of highly saturated colors observed.

  DOI：

  10.1021/om200644e
• 作为产物：
  描述：

  (E)-1-(2-hydroxyphenyl)-3-(ferrocenyl)prop-2-en-1-one 在 NaH 、 AgCF₃SO₃ 作用下， 以 四氢呋喃 为溶剂， 以90%的产率得到2-ferrocenyl-chromen-4-one
  参考文献：
  名称：

  Synthesis of cytotoxic ferrocenyl flavones via a ferricenium-mediated 1,6-oxidative cyclization

  摘要：

  2′-hydroxy ferrocenyl chalcones 的二茂铁基团氧化激活了不饱和酮的β位，使其受到亲核攻击，从而产生了首例二茂铁基黄酮。这些化合物对 B16 黑色素瘤细胞的细胞毒性明显高于其有机类似物，IC50 值在低微摩尔范围内。

  DOI：

  10.1039/c0cc01290d

文献信息

• Ferrocene-embedded flavonoids targeting the Achilles heel of multidrug-resistant cancer cells through collateral sensitivity
  作者：Basile Pérès、Rachad Nasr、Malik Zarioh、Florine Lecerf-Schmidt、Attilio Di Pietro、Hélène Baubichon-Cortay、Ahcène Boumendjel

  DOI：10.1016/j.ejmech.2017.02.064

  日期：2017.4

  to develop anticancer agents acting selectively against resistant tumor cells, we investigated ferrocene embedded into chalcone, aurone and flavone skeletons. These compounds were conceived and then investigated based on the concept of collateral sensitivity, where the target is the Achilles Heel of cancer cells overexpressing the multidrug ABC transporter MRP1. The 14 synthesized compounds were evaluated

  为了开发选择性对抗耐药肿瘤细胞的抗癌药，我们研究了嵌入查耳酮，金酮和黄酮骨架中的二茂铁。构想了这些化合物，然后根据附带敏感性的概念进行了研究，其中的靶标是过度表达多药ABC转运蛋白MRP1的癌细胞的跟腱。评价了14种合成化合物从过表达MRP1的肿瘤细胞中诱导谷胱甘肽（GSH）外排的能力。当在5和20μM下进行测试时，发现每个系列中的至少一种化合物是GSH外排的高度诱导剂。分别在敏感和耐药细胞系上评估了诱导GSH高流出的不同化合物，发现其中两种属于黄酮类，对耐药癌细胞具有更高的细胞毒性，最佳选择比> 9.1。我们的结果为进一步优化奠定了化学和生物学基础。
• Ferrocenyl flavonoids
  申请人：Centre National de la Recherche Scientifique (CNRS)

  公开号：EP2368895A1

  公开（公告）日：2011-09-28

  The present invention relates to new ferrocenyl flavonoids, processes for preparing them, pharmaceutical compositions containing them and their uses as pharmaceuticals.

  本发明涉及新的二茂铁基黄酮类化合物，以及制备它们的方法，含有它们的药物组合物以及它们作为药物的用途。
• Ferrocenyl flavonoid-induced morphological modifications of endothelial cells and cytotoxicity against B16 murine melanoma cells
  作者：Jean-Philippe Monserrat、Keshri Nath Tiwari、Lionel Quentin、Pascal Pigeon、Gérard Jaouen、Anne Vessières、Guy G. Chabot、Elizabeth A. Hillard

  DOI：10.1016/j.jorganchem.2012.12.031

  日期：2013.6

  With the aim of improving the cytotoxic and vascular disrupting activities of flavonoids, several classes of ferrocenyl-modified flavonoids were prepared and tested on cancer and endothelial cells. Three tenmember series of ferrocenyl flavonoids: chalcones ((E)-1-(R-2'-hydroxypheny1)-3-ferrocenylprop-2-en-1-ones), aurones ((Z)-R-2-(ferrocenylidene)benzofuran-3-ones) and flavones (R-2-ferrocenyl-chromen-4-ones) were synthesized by recently reported methods. Three ferrocenyl flavonols (R-3-hydroxy2-ferrocenyl-chromen-4-ones) and four ferrocenyl flavanones (3-ferrocenylmethylidenyl-R-2-phenyl-chroman-4-ones) were also obtained. All compounds were evaluated for their cytotoxic effects on a cancer cell line (B16 murine melanoma) and for their morphological effects on endothelial cells (EAhy 926). Some interesting structure-activity relationships were disclosed: of all the compounds, the halogen-substituted aurones showed the best cytotoxic activity, with IC50 values ranging between 12 and 18 mu M. Ferrocenyl flavonols and ferrocenyl flavanones with substitution in the 3-position (-OH and =C-Fc respectively) were not active against cancer or endothelial cells. Some of the ferrocenyl flavones caused the endothelial cells to adopt a round shape ("rounding up") at submicromolar concentrations, which can be predictive of vascular disrupting activity. The most morphologically active flavones showed only moderate cytotoxicity against cancer cells, indicating that they may primarily act as antivascular agents. (C) 2013 Elsevier B.V. All rights reserved.
• Ferrocenyl-Appended Aurone and Flavone: Which Possesses Higher Inhibitory Effects on DNA Oxidation and Radicals?
  作者：Jia-Feng Chen、Zai-Qun Liu

  DOI：10.1021/tx500405b

  日期：2015.3.16

  The aim of the present work was to compare the antioxidative effect of the ferrocenyl-appended aurone with that of ferrocenyl-appended flavone; therefore, nine aurones together with the flavone-type analogues were synthesized by using chalcone as the reactant. The radical-scavenging property was evaluated by reacting with the 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS'), 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH), and galvinoxyl radical, respectively. The cytotoxicity was estimated by inhibiting 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH)-induced oxidation of DNA. It was found that the introduction of the ferrocenyl group remarkably increased the radical-scavenging activities of aurone and flavone. Especially, the ferrocenyl group in flavones can quench radicals even in the absence of the phenolic hydroxyl group, while ferrocenyl-appended aurones can efficiently protect DNA against AAPH-induced oxidation. Therefore, the antioxidative effect was generated by the ferrocenyl group and enhanced by the electron-donating group attaching to the para-position of the ferrocenyl group. Introducing the ferrocenyl group into natural compounds may be a useful strategy for increasing the anticoddative effectiveness.
• [EN] FERROCENYL FLAVONOIDS<br/>[FR] FLAVONOÏDES COMPRENANT UN GROUPE FERROCÉNYLE
  申请人：CENTRE NAT RECH SCIENT

  公开号：WO2011107572A8

  公开（公告）日：2012-04-26