(R)-2-(2-hydroxyphenyl)-2,3-dihydroquinazolin-4(1H)-one

• 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: (R)-2-(2-hydroxyphenyl)-2,3-dihydroquinazolin-4(1H)-one
• 英文别名: (2R)-2-(2-hydroxyphenyl)-2,3-dihydro-1H-quinazolin-4-one
• 化学式: C₁₄H₁₂N₂O₂
• 分子量: 240.261
• InChiKey: BXIPTFOWLQHBIH-CYBMUJFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  61.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-苯基双(三氟甲烷磺酰)亚胺 、 (R)-2-(2-hydroxyphenyl)-2,3-dihydroquinazolin-4(1H)-one 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 以84%的产率得到
  参考文献：
  名称：

  Asymmetric Synthesis of 2,3-Dihydro-2-arylquinazolin-4-ones: Methodology and Application to a Potent Fluorescent Tubulin Inhibitor with Anticancer Activity

  摘要：

  For several decades the 2,3-dihydroquinazolinone (DHQZ) heterocycle has been known to possess a variety of important biological and medicinal properties. Despite the many interesting facets of these molecules, synthetic access to nonracemic DHQZ analogues has remained elusive. Herein, we disclose a synthetic route that allows access to either enantiomer of a variety of DHQZ derivatives. We illustrate the utility of this chemistry with the asymmetric preparation and biological evaluation of a new chiral fluorescent tubulin binding agent with extremely potent antiproliferative properties against human cancer cells. A computational rationale for the increased potency of the (S)-enantiomer over the (R)-enantiomer is given, based on the crystal structure of alpha,beta-tubulin complexed with colchicine. Taking advantage of the inherent fluorescence of these molecules, confocal images of GMC-5-193 (compound 7) in the cytoplasm of human melanoma cells (MDA-MB-435) cells are presented.

  DOI：

  10.1021/jm800271c
• 作为产物：
  描述：

  2-((R)-4-oxo-1,2,3,4-tetrahydroquinazolin-2-yl)phenyl (S)-2-((tert-butoxycarbonyl)amino)-3,3-dimethylbutanoate 在 一水合肼 作用下， 以 四氢呋喃 为溶剂， 以94%的产率得到(R)-2-(2-hydroxyphenyl)-2,3-dihydroquinazolin-4(1H)-one
  参考文献：
  名称：

  Asymmetric Synthesis of 2,3-Dihydro-2-arylquinazolin-4-ones: Methodology and Application to a Potent Fluorescent Tubulin Inhibitor with Anticancer Activity

  摘要：

  For several decades the 2,3-dihydroquinazolinone (DHQZ) heterocycle has been known to possess a variety of important biological and medicinal properties. Despite the many interesting facets of these molecules, synthetic access to nonracemic DHQZ analogues has remained elusive. Herein, we disclose a synthetic route that allows access to either enantiomer of a variety of DHQZ derivatives. We illustrate the utility of this chemistry with the asymmetric preparation and biological evaluation of a new chiral fluorescent tubulin binding agent with extremely potent antiproliferative properties against human cancer cells. A computational rationale for the increased potency of the (S)-enantiomer over the (R)-enantiomer is given, based on the crystal structure of alpha,beta-tubulin complexed with colchicine. Taking advantage of the inherent fluorescence of these molecules, confocal images of GMC-5-193 (compound 7) in the cytoplasm of human melanoma cells (MDA-MB-435) cells are presented.

  DOI：

  10.1021/jm800271c

文献信息

• Enantioselective synthesis of dihydroquinazolinone derivatives catalyzed by a chiral organocatalyst
  作者：Siva Ayyanar、Ponmuthu Kottala Vijaya、Madhappan Mariyappan、Veeramanoharan Ashokkumar、Velu Sadhasivam、Sankar Balakrishnan、Chithiraikumar Chinnadurai、Sepperumal Murugesan

  DOI：10.1039/c7nj00538e

  日期：——

  2-aminobenzamide and aldehydes, catalyzed by a novel chiral organocatalyst, was realized. The organocatalyst was found to be very effective and highly enantioselective for such cascade reactions at room temperature, affording 2,3-dihydroquinazolinones in excellent yields (up to 99%) with enantiomeric excesses of up to 97%. The best level of stereocontrol was obtained for aromatic/aliphatic aldehydes with ortho

  实现了新型手性有机催化剂催化的2-氨基苯甲酰胺与醛类的不对称缩合/胺加成级联序列。发现有机催化剂对于这种在室温下的级联反应是非常有效的和高度对映选择性的，以优异的产率（高达99％）提供了2，3-二氢喹唑啉酮，对映体过量高达97％。对于具有邻位，对位或间位取代基的芳族/脂肪族醛，可获得最佳的立体控制水平。
• Conformational Control of Organocatalyst in Strongly Brønsted‐Acidic Metal‐Organic Frameworks for Enantioselective Catalysis
  作者：Hong Jiang、Xiangxiang Zhao、Wenqiang Zhang、Yan Liu、Haiyang Li、Yong Cui

  DOI：10.1002/anie.202214748

  日期：2023.1.9

  (IDP) into two Dy metal-organic frameworks (MOFs) allows controlling the organocatalyst conformations and local chiral microenvironments. The MOF containing the 4-connected IDPs has a less compact shape and can be an efficient and recyclable heterogeneous Brønsted acid catalyst for the challenging asymmetric O,O-acetalization of diol and aldehyde with up to 96 % ee.

  将手性 1,1'-双酚基亚氨基二磷酸 (IDP) 网状化为两个 Dy 金属有机框架 (MOF) 可以控制有机催化剂构象和局部手性微环境。包含 4-connected IDPs 的 MOF 具有不太紧凑的形状，可以作为一种高效且可回收的非均相 Brønsted 酸催化剂，用于具有挑战性的二醇和醛的不对称 O, O-缩醛化，ee 高达 96%。