(-)-methyl (1R,2R,3S,3aR,8bS)-3a-(4-bromophenyl)-1,8b-dihydroxy-6,8-dimethoxy-3-phenyl-2,3,3a,8b-tetrahydro-1Hcyclopenta[b]benzofuran-2-carboxylate | 1139251-48-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: (-)-methyl (1R,2R,3S,3aR,8bS)-3a-(4-bromophenyl)-1,8b-dihydroxy-6,8-dimethoxy-3-phenyl-2,3,3a,8b-tetrahydro-1Hcyclopenta[b]benzofuran-2-carboxylate
• 英文别名: methyl (1R,2R,3S,3aR,8bS)-3a-(4-bromophenyl)-1,8b-dihydroxy-6,8-dimethoxy-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxylate
• CAS: 1139251-48-1
• 化学式: C₂₇H₂₅BrO₇
• 分子量: 541.395
• InChiKey: KVSUQUWGPPVBJE-PXIJUOARSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  94.4
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (-)-methyl (1R,2R,3S,3aR,8bS)-3a-(4-bromophenyl)-1,8b-dihydroxy-6,8-dimethoxy-3-phenyl-2,3,3a,8b-tetrahydro-1Hcyclopenta[b]benzofuran-2-carboxylate 在 氨 作用下， 以 甲醇 为溶剂， 反应 36.0h， 以30%的产率得到(1R,2R,3S,3aR,8bS)-3a-(4-bromophenyl)-1,8b-dihydroxy-6,8-dimethoxy-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxamide
  参考文献：
  名称：

  Novel Flavaglines Displaying Improved Cytotoxicity

  摘要：

  Novel flavagline analogues were synthesized and examined with respect to their cytotoxicity Structural features critical to the potential of this class of anticancer natural products wet e unraveled We demonstrated, in particular, that the introduction of substituants at C-2 has a deleterious effect on multidrug resistance Replacement of the hydroxy at C-1 by an aminoformyl with the opposite configuration enhances the cytotoxicity and led to a compound that reduces tumors growth in an allograft model at nontoxic doses

  DOI：

  10.1021/jm101318b
• 作为产物：
  描述：

  在 sodium methylate 、 溶剂黄146 、 tetramethylammonium triacetoxyborohydride 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 0.33h， 生成 (-)-methyl (1R,2R,3S,3aR,8bS)-3a-(4-bromophenyl)-1,8b-dihydroxy-6,8-dimethoxy-3-phenyl-2,3,3a,8b-tetrahydro-1Hcyclopenta[b]benzofuran-2-carboxylate
  参考文献：
  名称：

  Novel Flavaglines Displaying Improved Cytotoxicity

  摘要：

  Novel flavagline analogues were synthesized and examined with respect to their cytotoxicity Structural features critical to the potential of this class of anticancer natural products wet e unraveled We demonstrated, in particular, that the introduction of substituants at C-2 has a deleterious effect on multidrug resistance Replacement of the hydroxy at C-1 by an aminoformyl with the opposite configuration enhances the cytotoxicity and led to a compound that reduces tumors growth in an allograft model at nontoxic doses

  DOI：

  10.1021/jm101318b

文献信息

• Rocaglaol derivatives as cardioprotectant agents
  申请人：Université Louis Pasteur

  公开号：EP2189453A1

  公开（公告）日：2010-05-26

  The present invention discloses new rocaglaol derivatives and the use of rocaglaol derivatives to prevent or to limit the cardiotoxicity of an antineoplastic agent, in particular to prevent or to limit the apoptosis of cardiomyocytes induced by such agent.

  本发明公开了新的罗钙素衍生物及其用途，用于预防或限制抗肿瘤剂的心脏毒性，特别是用于预防或限制由该剂诱导的心肌细胞凋亡。
• Biomimetic Kinetic Resolution: Highly Enantio- and Diastereoselective Transfer Hydrogenation of Aglain Ketones To Access Flavagline Natural Products
  作者：Steven D. Stone、Neil J. Lajkiewicz、Luke Whitesell、Ahmed Hilmy、John A. Porco

  DOI：10.1021/ja511728b

  日期：2015.1.14

  We have previously reported asymmetric syntheses and absolute configuration assignments of the aglains (+)-ponapensin and (+)-elliptifoline and proposed a biosynthetic kinetic resolution process to produce enantiomeric rocaglamides and aglains. Herein, we report a biomimetic approach for the synthesis of enantiomerically enriched aglains and rocaglamides via kinetic resolution of a bridged ketone utilizing

  我们之前报道了 aglains (+)-ponapensin 和 (+)-elliptifoline 的不对称合成和绝对构型分配，并提出了一种生物合成动力学拆分过程来生产对映体罗卡酰胺和 aglains。在此，我们报告了一种仿生方法，通过利用对映选择性转移氢化作用的桥酮的动力学拆分来合成对映体富集的阿格兰和罗卡酰胺。该方法已用于合成和确认嘧啶酮罗卡酰胺 (+)-aglaistatin 和 (−)-aglaroxin C 的绝对立体化学。此外，还分析了每种代谢物的对映体和外消旋体的热休克反应抑制、细胞毒性。和翻译抑制。
• ROCAGLAOL DERIVATIVES AS CARDIOPROTECTANT AGENTS AND AS ANTINEOPLASTIC AGENTS
  申请人：Desaubry Laurent

  公开号：US20120101153A1

  公开（公告）日：2012-04-26

  The present invention discloses new rocaglaol derivatives and the use of rocaglaol derivatives to prevent or to limit the cardiotoxicity of an antineoplastic agent, in particular to prevent or to limit the apoptosis of cardiomyocytes induced by such agent.

  本发明揭示了新的洛卡格洛衍生物，并使用洛卡格洛衍生物来预防或限制抗肿瘤药物的心脏毒性，特别是预防或限制由该药物引起的心肌细胞凋亡。
• Halogenated Rocaglate Derivatives: Pan-antiviral Agents against Hepatitis E Virus and Emerging Viruses
  作者：Catherine Victoria、Göran Schulz、Mara Klöhn、Saskia Weber、Cora M. Holicki、Yannick Brüggemann、Miriam Becker、Gisa Gerold、Martin Eiden、Martin H. Groschup、Eike Steinmann、Andreas Kirschning

  DOI：10.1021/acs.jmedchem.3c01357

  日期：2024.1.11

  The synthesis of a library of halogenated rocaglate derivatives belonging to the flavagline class of natural products, of which silvestrol is the most prominent example, is reported. Their antiviral activity and cytotoxicity profile against a wide range of pathogenic viruses, including hepatitis E, Chikungunya, Rift Valley Fever virus and SARS-CoV-2, were determined. The incorporation of halogen substituents

  据报道，属于黄黄素类天然产物的卤代罗卡格酯衍生物库的合成，其中西维甾醇是最突出的例子。确定了它们对多种致病病毒的抗病毒活性和细胞毒性，包括戊型肝炎、基孔肯雅热、裂谷热病毒和 SARS-CoV-2。在4'、6和8位上引入卤素取代基对罗卡格拉特的抗病毒活性有显着影响，其中一些甚至比CR-31-B和西维甾醇显示出增强的活性。
• Synthetic Analogue of Rocaglaol Displays a Potent and Selective Cytotoxicity in Cancer Cells: Involvement of Apoptosis Inducing Factor and Caspase-12
  作者：Frédéric Thuaud、Yohann Bernard、Gülen Türkeri、Ronan Dirr、Geneviève Aubert、Thierry Cresteil、Aurélie Baguet、Catherine Tomasetto、Yuri Svitkin、Nahum Sonenberg、Canan G. Nebigil、Laurent Désaubry

  DOI：10.1021/jm900365v

  日期：2009.8.27

  Flavaglines constitute a family of natural anticancer compounds. We present here 3 (FL3), the first synthetic flavagline that inhibits cell proliferation and viability (IC50 approximate to 1 nM) at lower doses than did the parent compound, racemic rocaglaol. Compound 3 enhanced doxorubicin cytotoxicity in HepG2 cells and retained its potency against. adriamycin-resistant cell lines without inducing cardiomyocyte toxicity. Compound 3 induced apoptosis of HL60 and Hela cells by triggering the translocation of Apoptosis Inducing Factor (AIF) and caspase-12 to the nucleus. A fluorescent conjugate of 3 accumulated ill endoplasmic reticulum (ER), suggesting that flavaglines bind to their target in the ER. where it triggers a cascade of events that leads to the translocation of AIF and caspase-12 to the nucleus and probably inhibition of eIF4A. Our studies highlight structural features critical to their antineoplastic potential and suggest that these compounds would retain their activity in cells refractory to caspase activation.