4‐(5‐acetoxy‐7‐hydroxy‐4‐oxo‐4H‐chromen‐2‐yl)‐1,2‐phenylene diacetate

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: 4‐(5‐acetoxy‐7‐hydroxy‐4‐oxo‐4H‐chromen‐2‐yl)‐1,2‐phenylene diacetate
• 英文别名: 3′,4′,5-triacetylluteolin；3',4',5-triacetylluteolin
• 化学式: C₂₁H₁₆O₉
• 分子量: 412.353
• InChiKey: MFAHRNBAIWYGJY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.94
• 重原子数：
  30.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  129.34
• 氢给体数：
  1.0
• 氢受体数：
  9.0

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	luteolin tetraacetate	1061-93-4	C23H18O10	454.39
  木犀草素	2-(3,4-Dihydroxy-phenyl)-5,7-dihydroxy-chromen-4-on	491-70-3	C15H10O6	286.241

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	N-((phenoxy)((5-acetoxy-2-(3,4-diacetoxyphenyl)-4-oxo-4H-chromene-7-yl)oxy)phosphoryl)glycine methyl ester	——	C30H26NO13P	639.509
  ——	N-((phenoxy)((5-acetoxy-2-(3,4-diacetoxyphenyl)-4-oxo-4H-chromene-7-yl)oxy)phosphoryl)-L-alanine methyl ester	——	C31H28NO13P	653.536
  ——	N-((phenoxy)((5-acetoxy-2-(3,4-diacetoxyphenyl)-4-oxo-4H-chromene-7-yl)oxy)phosphoryl)-L-leucine methyl ester	——	C34H34NO13P	695.617
  ——	N-((phenoxy)((5-acetoxy-2-(3,4-diacetoxyphenyl)-4-oxo-4H-chromene-7-yl)oxy)phosphoryl)-L-phenylalanine methyl ester	——	C37H32NO13P	729.634
  ——	2-(3,4-dihydroxyphenyl)-5-hydroxy-7-morpholino-4H-chromen-4-one	1610737-73-9	C19H17NO6	355.347
  ——	N-((phenoxy)((5-hydroxy-2-(3,4-dihydroxyphenyl)-4-oxo-4H-chromene-7-yl)oxy)phosphoryl)-L-leucine methyl ester	——	C28H28NO10P	569.505
  ——	N-((phenoxy)((5-hydroxy-2-(3,4-dihydroxyphenyl)-4-oxo-4H-chromene-7-yl)oxy)phosphoryl)-L-valine methyl ester	——	C27H26NO10P	555.478
  ——	N-((phenoxy)((5-hydroxy-2-(3,4-dihydroxyphenyl)-4-oxo-4H-chromene-7-yl)oxy)phosphoryl)-L-phenylalanine methyl ester	——	C31H26NO10P	603.522

反应信息

• 作为反应物：
  描述：

  4‐(5‐acetoxy‐7‐hydroxy‐4‐oxo‐4H‐chromen‐2‐yl)‐1,2‐phenylene diacetate 在 氨 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 10.0h， 生成 2-(3,4-dihydroxyphenyl)-5-hydroxy-4-oxo-4H-chromen-7-yl-4-methylbenzenesulfonate
  参考文献：
  名称：

  Design and discovery of flavonoid-based HIV-1 integrase inhibitors targeting both the active site and the interaction with LEDGF/p75

  摘要：

  HIV integrase (IN) is an essential enzyme for the viral replication. Currently, three IN inhibitors have been approved for treating HIV-1 infection. All three drugs selectively inhibit the strand transfer reaction by chelating a divalent metal ion in the enzyme active site. Flavonoids are a well-known class of natural products endowed with versatile biological activities. Their beta-ketoenol or catechol structures can serve as a metal chelation motif and be exploited for the design of novel IN inhibitors. Using the metal chelation as a common pharmacophore, we introduced appropriate hydrophobic moieties into the flavonol core to design natural product-based novel IN inhibitors. We developed selective and efficient syntheses to generate a series of mono 3/5/7/3'/4'-substituted flavonoid derivatives. Most of these new compounds showed excellent HIV-1 IN inhibitory activity in enzyme-based assays and protected against HIV-1 infection in cell-based assays. The 7-morpholino substituted 7c showed effective antiviral activity (EC50 = 0.826 mu g/mL) and high therapeutic index (TI > 242). More significantly, these hydroxyflavones block the IN-LEDGF/p75 interaction with low-to sub-micromolar IC50 values and represent a novel scaffold to design new generation of drugs simultaneously targeting the catalytic site as well as protein-protein interaction domains. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.04.016
• 作为产物：
  描述：

  木犀草素 在 吡啶 、 咪唑 、 苯硫酚 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 为溶剂， 反应 3.0h， 生成 4‐(5‐acetoxy‐7‐hydroxy‐4‐oxo‐4H‐chromen‐2‐yl)‐1,2‐phenylene diacetate
  参考文献：
  名称：

  C-7 和 C-8 木犀草素衍生物作为流感核酸内切酶抑制剂的合成和体外评价

  摘要：

  具有核酸内切酶活性的流感聚合酶 PA 亚基部分是抗流感治疗的靶点，包括 FDA 批准的药物 Xofluza。核酸内切酶抑制剂的一般特征是它们能够螯合位于酶催化位点的Mg 2+或 Mn 2+离子。以前，我们筛选了一组黄酮类化合物以抑制 PA，发现木犀草素及其 C-葡萄糖苷定向蛋白是有效的抑制剂。通过结构分析，我们确定 3',4'-二羟基苯基部分的存在是亚微摩尔抑制活性的关键特征。在这里，我们报告了后续调查的结果，该调查探索了木犀草素 C-7 和 C-8 位置的结构变化。实验 IC 50值由 AlphaScreen 技术确定。最有效的抑制剂是 C-8 衍生物，其抑制效力与木犀草素相当。木犀草素的 C-7 羟基部分的生物等排置换产生了一系列具有低一个数量级抑制效力的化合物。使用 X 射线晶体学，我们分别以 1.9 Å 和 2.2 Å 的分辨率解析了野生型 PA-N 末端结构域及其 I38T 突变体与

  DOI：

  10.3390/ijms22147735

文献信息

• Phosphoramidate protides of five flavones and their antiproliferative activity against HepG2 and L-O2 cell lines
  作者：Yue-qing Li、Fei Yang、Liu Wang、Zhi Cao、Tian-jiao Han、Zhe-ang Duan、Zhen Li、Wei-jie Zhao

  DOI：10.1016/j.ejmech.2016.02.012

  日期：2016.4

  A series of flavone-7-phosphoramidate derivatives were synthesized and tested for their antiproliferative activity in vitro against human hepatoma cell line HepG2 and human normal hepatic cell line L-O2. Compound 8d, 16d and 17d, incorporating the amino acid alanine, exhibited high inhibitory activity on HepG2 cell line with IC50 values of 9.0 mu mol/L, 5.5 mu mol/L and 6.6 mu mol/L. The introduction of acyl groups played a pivotal role in the selective inhibition toward human hepatoma HepG2 cells, except for compound 8a, 9a and 16b. Compound 8d, 16d and 17d could significantly induce G2/M arrest in HepG2 cells. Specially, Compound 16d could lead early apoptosis in HepG2 cells. (C) 2016 Elsevier Masson SAS. All rights reserved.
• Design and discovery of flavonoid-based HIV-1 integrase inhibitors targeting both the active site and the interaction with LEDGF/p75
  作者：Bo-Wen Li、Feng-Hua Zhang、Erik Serrao、Huan Chen、Tino W. Sanchez、Liu-Meng Yang、Nouri Neamati、Yong-Tang Zheng、Hui Wang、Ya-Qiu Long

  DOI：10.1016/j.bmc.2014.04.016

  日期：2014.6

  HIV integrase (IN) is an essential enzyme for the viral replication. Currently, three IN inhibitors have been approved for treating HIV-1 infection. All three drugs selectively inhibit the strand transfer reaction by chelating a divalent metal ion in the enzyme active site. Flavonoids are a well-known class of natural products endowed with versatile biological activities. Their beta-ketoenol or catechol structures can serve as a metal chelation motif and be exploited for the design of novel IN inhibitors. Using the metal chelation as a common pharmacophore, we introduced appropriate hydrophobic moieties into the flavonol core to design natural product-based novel IN inhibitors. We developed selective and efficient syntheses to generate a series of mono 3/5/7/3'/4'-substituted flavonoid derivatives. Most of these new compounds showed excellent HIV-1 IN inhibitory activity in enzyme-based assays and protected against HIV-1 infection in cell-based assays. The 7-morpholino substituted 7c showed effective antiviral activity (EC50 = 0.826 mu g/mL) and high therapeutic index (TI > 242). More significantly, these hydroxyflavones block the IN-LEDGF/p75 interaction with low-to sub-micromolar IC50 values and represent a novel scaffold to design new generation of drugs simultaneously targeting the catalytic site as well as protein-protein interaction domains. (C) 2014 Elsevier Ltd. All rights reserved.
• Synthesis and In Vitro Evaluation of C-7 and C-8 Luteolin Derivatives as Influenza Endonuclease Inhibitors
  作者：Robert Reiberger、Kateřina Radilová、Michal Kráľ、Václav Zima、Pavel Majer、Jiří Brynda、Martin Dračínský、Jan Konvalinka、Milan Kožíšek、Aleš Machara

  DOI：10.3390/ijms22147735

  日期：——

  The part of the influenza polymerase PA subunit featuring endonuclease activity is a target for anti-influenza therapies, including the FDA-approved drug Xofluza. A general feature of endonuclease inhibitors is their ability to chelate Mg2+ or Mn2+ ions located in the enzyme’s catalytic site. Previously, we screened a panel of flavonoids for PA inhibition and found luteolin and its C-glucoside orientin

  具有核酸内切酶活性的流感聚合酶 PA 亚基部分是抗流感治疗的靶点，包括 FDA 批准的药物 Xofluza。核酸内切酶抑制剂的一般特征是它们能够螯合位于酶催化位点的Mg 2+或 Mn 2+离子。以前，我们筛选了一组黄酮类化合物以抑制 PA，发现木犀草素及其 C-葡萄糖苷定向蛋白是有效的抑制剂。通过结构分析，我们确定 3',4'-二羟基苯基部分的存在是亚微摩尔抑制活性的关键特征。在这里，我们报告了后续调查的结果，该调查探索了木犀草素 C-7 和 C-8 位置的结构变化。实验 IC 50值由 AlphaScreen 技术确定。最有效的抑制剂是 C-8 衍生物，其抑制效力与木犀草素相当。木犀草素的 C-7 羟基部分的生物等排置换产生了一系列具有低一个数量级抑制效力的化合物。使用 X 射线晶体学，我们分别以 1.9 Å 和 2.2 Å 的分辨率解析了野生型 PA-N 末端结构域及其 I38T 突变体与