8-fluoroindolo[2,1-b]quinazoline-6,12-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 8-fluoroindolo[2,1-b]quinazoline-6,12-dione
• 英文别名: 8-fluorotryptanthrin
• 化学式: C₁₅H₇FN₂O₂
• 分子量: 266.231
• InChiKey: UXBGZQXHNVNPFT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  20
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  49.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  8-fluoroindolo[2,1-b]quinazoline-6,12-dione 在 一水合肼 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 以71%的产率得到8-fluoro-6-hydrazonoindolo[2,1-b]quinazolin-12(6H)-one
  参考文献：
  名称：

  Design, synthesis and biological evaluation of 8-substituted-6-hydrazonoindolo[2,1- b ]quinazolin-12(6 H )-one scaffolds as potential cytotoxic agents: IDO-1 targeting molecular docking studies

  摘要：

  Herein, we have reported the synthesis of 18 novel 8-substituted tryptanthrin analogues based on our earlier work. All these tryptanthrin analogues were well characterized by H-1 & C-13 NMR, FT-IR, Mass Spectrometry and Elemental Analysis. All these 8-substituted analogues were screened for their anti-oxidant activity by DPPH radical scavenging assay. Out of all the tested compounds, T-11, T-12,T-17 and T-18 showed potent anti-oxidant activity. The anti-cancer activity have been performed by using MTT assay protocol and their results depicts that compounds having the 4-pyridyl or 4-carboxyphenyl substituents at the 8th position of the tryptanthrin framework are found to be the most promising cytotoxic agent against A549, MCF-7 and HeLa human cancer cell lines compared to others as well as with the standard drug cisplatin. Moreover, the comparative molecular docking studies against the three protein receptors IDO1, EGFR and HER2 strongly suggested that IDO1 is the best target protein, which exhibits lowest binding energies of -11.73 and -11.61 kcal mol(-1) for T-11 and T-12 scaffolds, respectively towards the in vitro anti-cancer activity. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.08.064
• 作为产物：
  描述：

  4-fluoroisonitrosoacetanilide 在 硫酸 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.33h， 生成 8-fluoroindolo[2,1-b]quinazoline-6,12-dione
  参考文献：
  名称：

  抗肿瘤剂色氨酸的合成与评价

  摘要：

  在这里，通过色氨酸和仲胺在温和的反应条件下反应快速制备 N-取代的色氨酸类似物，开发了一种有效和方便的方法。通过MTT测定法测试所有化合物在癌细胞系中的抗肿瘤活性。结果表明，其中一些对人肿瘤细胞系 A549、HCT116、MDA-MB-231 表现出抗肿瘤活性，IC 50平均值处于低微摩尔水平。具体而言，化合物3b剂量依赖性地诱导A549细胞中的G2/S细胞周期停滞和细胞凋亡。

  DOI：

  10.1016/j.tet.2021.132454

文献信息

• Direct Catalytic Asymmetric Synthesis of β-Hydroxy Acids from Malonic Acid
  作者：Hang Gao、Zhenli Luo、Pingjin Ge、Junqian He、Feng Zhou、Peipei Zheng、Jun Jiang

  DOI：10.1021/acs.orglett.5b02891

  日期：2015.12.18

  A nickel(II) catalyzed asymmetric synthesis of β-hydroxy acids from malonic acid and ketones was developed, revealing for the first time the synthetic utility of malonic acid in the construction of chiral carboxyl acids; importantly, the synthetic potential of this strategy was further demonstrated by the rapid construction of cephalanthrin A, phaitanthrin B, cruciferane, and rice metabolites.

  开发了镍（II）催化由丙二酸和酮不对称合成β-羟基酸的方法，这首次揭示了丙二酸在手性羧酸的合成中的合成作用。重要的是，该方法的合成潜力通过快速构建头孢菌素A，紫杉醇B，十字花青素和大米代谢产物得到了进一步证明。
• Ni(II)-Catalyzed Enantioselective Synthesis of β-Hydroxy Esters with Carboxylate Assistance
  作者：Na Wang、Hongxin Liu、Hang Gao、Jiafeng Zhou、Longzhangdi Zheng、Juan Li、Hong-Ping Xiao、Xinhua Li、Jun Jiang

  DOI：10.1021/acs.orglett.9b02297

  日期：2019.9.6

  decarboxylative aldol reaction between malonic acid half-oxyesters and various carbonyls with carboxylate assistance was developed, affording structurally diverse β-hydroxy esters with good yields and enantioselectivities under mild conditions. Importantly, the broad substrate scope of this methodology enabled rapid accesses to several natural products and their analogues as exemplified by phenylpropanoid, phaitanthrin

  建立了Ni-恶唑啉配合物催化丙二酸半含氧酸酯和各种羰基在羧酸酯辅助下的不对称脱羧醛醇缩合反应，在温和条件下以良好的收率和对映选择性提供了结构多样的β-羟基酯。重要的是，这种方法的广泛的底物范围使人们能够快速获得几种天然产物及其类似物，例如苯丙烷，类赤霉素B和邻苯二甲酸酯。
• Synthesis of 6-Alkynyl-6-hydroxyindoloquinazolinone Scaffolds via Copper-Catalyzed Alkynylation of Tryptanthrins
  作者：Yu Guo、Ebrahim-Alkhalil M. A. Ahmed、De-Kun Ma、Jun Jiang、Hongxin Liu、Xinhua Li、Juan Li、Hong-Ping Xiao

  DOI：10.1055/a-1533-1080

  日期：2021.9

  alkynes under mild reaction conditions. The developed method provides an array of synthetic building blocks of 6-alkynyl-6-hydroxyindoloquinazolinone compounds in moderate to good yields with varied functional group compatibility. Furthermore, the obtained adducts can be smoothly converted into versatile building blocks via hydrogenation, hydration, and further Sonogashira coupling transformations.

  我们报道了在温和的反应条件下，铜催化的色氨酸与末端炔烃的直接炔化反应。所开发的方法以中等至良好的产率提供了一系列 6-炔基-6-羟基吲哚并喹唑啉酮化合物的合成结构单元，具有不同的官能团兼容性。此外，所获得的加合物可以通过氢化、水合和进一步的 Sonogashira 偶联转化顺利转化为通用结构单元。
• Synthesis of substituted tryptanthrin via aryl halides and amines as antitumor and anti-MRSA agents
  作者：Xudong Zheng、Baolong Hou、Rui Wang、Yinyin Wang、Cuiling Wang、Huan Chen、Li Liu、Jilin Wang、Xiumei Ma、Jianli Liu

  DOI：10.1016/j.tet.2019.05.030

  日期：2019.11

  tryptanthrin (indolo[2,1-b]quinazoline-6,12-dione), and its analogues are found to exhibit potent antitumor and anti-MRSA activities. An efficient and convenient method has been developed for the synthesis of tryptanthrin D-ring derivatives through the reaction of substituted tryptanthrins and secondary amines in moderate to good yields. Some of the new compounds exhibited antitumor activities against the human

  发现天然生物碱类胰蛋白酶（吲哚[2,1-b]喹唑啉-6,12-二酮）及其类似物表现出有效的抗肿瘤和抗-MRSA活性。已经开发了一种有效且方便的方法，该方法通过使取代的色胺酮与仲胺反应以中等至良好的产率合成色胺酮D-环衍生物。一些新化合物对人肿瘤细胞系A549，HCT116和MDA-MB-231表现出抗肿瘤活性，低微摩尔水平的平均IC 50值。此外，某些化合物显示出优异的抗MRSA活性，并且比万古霉素更有效，Mu50，RN4220和Newman菌株的MIC值为0.31–1.25μg/ mL。
• Switching of Enantioselectivity in the Cu-Catalyzed Asymmetric Decarboxylative Aldol Reaction of Tryptanthrin with <i>β-</i>Keto Acids: An Unexpected Counteranion Effect
  作者：Fang-Fang Feng、Xue-Qi Wang、Long Sun、Chi Wai Cheung、Jing Nie、Jun-An Ma

  DOI：10.1021/acs.orglett.1c01315

  日期：2021.6.4

  Cu-bisoxazoline-catalyzed enantioselective decarboxylative aldol reaction of tryptanthrin with aryl-substituted β-keto acids is developed, providing a straightforward approach to deliver a series of phaitanthrin A analogues. Both enantiomers of the products can be obtained with good to high enantioselectivity in the presence of a single chiral ligand by simply changing the copper salts. Based on the

  开发了 Cu-双恶唑啉催化的色氨酸与芳基取代的β-酮酸的对映选择性脱羧醛醇反应，提供了一种直接的方法来提供一系列的苯菊酯 A 类似物。在单一手性配体存在下，通过简单地改变铜盐，可以以良好到高的对映选择性获得产物的两种对映异构体。基于手性 Cu(II)-双恶唑啉配合物的 X 射线晶体学分析，提出了初步的立体化学模型，以解释观察到的反阴离子诱导的对映选择性转换。