3-甲基-2-吗啉-4-基-2,3-二氢-1-苯并呋喃-5-醇 | 113297-22-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 香豆素
• 中文名称: 3-甲基-2-吗啉-4-基-2,3-二氢-1-苯并呋喃-5-醇
• 英文名称: 3-methyl-2-morpholin-4-yl-2,3-dihydro-benzofuran-5-ol
• 英文别名: 3-Methyl-2-morpholino-2,3-dihydrobenzofuran-5-ol；3-methyl-2-morpholin-4-yl-2,3-dihydro-1-benzofuran-5-ol
• CAS: 113297-22-6
• 化学式: C₁₃H₁₇NO₃
• 分子量: 235.283
• InChiKey: ATWPIRLSEMZQIO-UHFFFAOYSA-N

物化性质

• 沸点：
  370.6±42.0 °C(Predicted)
• 密度：
  1.237±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  41.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-甲基-2-吗啉-4-基-2,3-二氢-1-苯并呋喃-5-醇 在 盐酸 、 2,3-二氯-5,6-二氰基-1,4-苯醌 、 2-碘酰基苯甲酸 作用下， 以 四氢呋喃 、 水 、 甲苯 为溶剂， 反应 5.0h， 生成 3,8-dimethylnaphtho[1,2-b]furan-4,5-dione
  参考文献：
  名称：

  Discovery of quinone-directed antitumor agents selectively bioactivated by NQO1 over CPR with improved safety profile

  摘要：

  In this work, we mainly focused on discovering compounds with good selectivity for NQO1 over CPR. The NQO1-mediated two-electron reduction of compounds would kill cancer cells selectively, while CPR-mediated one-electron reduction would induce potential hepatotoxicity. Several novel quinone-directed antitumor agents were discovered as specific NQO1 substrates through structure-activity relationship studies. Among them, compound 3,7,8-trimethylnaphtho[1,2-b] furan-4,5-dione (12b) emerged as the most specific substrate of the two-electron oxidoreductase NQO1 and could hardly be reduced by CPR. It afforded the highest selectivity between NQO1/CPR (selectivity ratio = 6.37), much higher than the control beta-lapachone (selectivity ratio = 1.36), indicated 12b may possess superior safety profile. The electrochemical studies provided a reasonable explanation to the good selectivity toward NQO1. Molecular docking studies supported that 12b was capable of forming additional C-H... pi interactions with Trp105 and Phe178 residues compared to the control beta-lap. In addition, compound 12b was shown to kill cancer cells efficiently both in vitro and in vivo model. This work gave us a promising and novel scaffold for further investigation. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.02.004
• 作为产物：
  描述：

  4-propenyl-morpholine 在 对苯醌 作用下， 以 甲苯 为溶剂， 生成 3-甲基-2-吗啉-4-基-2,3-二氢-1-苯并呋喃-5-醇
  参考文献：
  名称：

  3-methyl-benzofuran-5-ol and its use in perfume compositions

  摘要：

  本发明涉及一种新型香气化合物3-甲基苯并呋喃-5-醇，以及通过添加足够的嗅觉可接受量的3-甲基苯并呋喃-5-醇来改善、增强或修改香气配方的方法。

  公开号：

  US09212336B2

文献信息

• Application of cation-π interactions in enzyme-substrate binding: Design, synthesis, biological evaluation, and molecular dynamics insights of novel hydrophilic substrates for NQO1
  作者：Qijie Gong、Quanwei Yu、Nan Wang、Jiabao Hu、Pengfei Wang、Fulai Yang、Tian Li、Qidong You、Xiang Li、Xiaojin Zhang

  DOI：10.1016/j.ejmech.2021.113515

  日期：2021.10

  Cation-π interaction is a type of noncovalent interaction formed between the π-electron system and the positively charged ion or moieties. In this study, we designed a series of novel NQO1 substrates by introducing aliphatic nitrogen-containing side chains to fit with the L-shaped pocket of NQO1 by the formation of cation-π interactions. Molecular dynamics (MD) simulation indicated that the basic N

  阳离子-π相互作用是π-电子系统与带正电的离子或部分之间形成的一种非共价相互作用。在这项研究中，我们通过引入脂肪族含氮侧链，通过形成阳离子-π 相互作用与 NQO1 的 L 形口袋相配合，设计了一系列新型 NQO1 底物。分子动力学 (MD) 模拟表明，NQO1 底物侧链中的碱性 N 原子在生理条件下易于质子化，可以与 NQO1 酶的 Phe232 和 Phe236 残基形成阳离子-π 相互作用。具有甲基哌嗪基取代基的化合物4被鉴定为最有效的 NQO1 底物，还原速率和催化效率为 1263 ± 61 μmol NADPH/min/μmol NQO1 和 2.8 ± 0.3 × 10 6 M -1 s -1分别。值得注意的是，与 β-lap (43 μg/mL) 相比，化合物4表现出增加的水溶性 (110 μg/mL)，尤其是在酸性条件下（pH = 3，溶解度 > 1000 μg/mL）。化合物4
• Preparation and dienophilicity of 3-methyl-4,5-benzofurandione
  作者：Junning Lee、Jin Tang、John K Snyder

  DOI：10.1016/s0040-4039(00)96317-2

  日期：——

  The o-quinone 3-methyl-4,5-benzofurandione, , was prepared in 94% overall yield from p-henzoquinone and 1-morpholino-propene. The cycloaddition chemistry of with several dienes was examined and found to proceed in good to excellent yields.

  所述Ô -quinone 3-甲基4,5-苯并呋喃，，在从94％的总收率制备p -henzoquinone和1吗啉代丙烯。对具有几个二烯的环加成化学进行了检查，发现收率良好。
• Three-Step One-Pot Process of 3-Methyl-5-Benzofuranol from Amine, Aldehydes, and <i>p</i>-Benzoquinone
  作者：Chaoming Liang、Maolin Sun、Xinyuan Shen、Chao Shan、Weijuan Wang、Ruihua Cheng、Jinxing Ye

  DOI：10.1021/acs.oprd.0c00507

  日期：2021.4.16

  3-Methyl-5-benzofuranol was prepared by a one-pot process from morpholine, propionaldehyde, and p-benzoquinone in 85–87% isolated yields. Avoiding the tedious multistep isolation and purification operations, this practical and efficient process dramatically enhanced the production efficiency as well as reduced the amount of chemical wastes of reaction. The scale-up results showed that the performance

  3-甲基-5-苯并呋喃醇是通过一锅法从吗啉，丙醛和对苯醌中制备的，分离产率为85-87％。避免了繁琐的多步分离和纯化操作，该实用而有效的过程极大地提高了生产效率，并减少了反应中化学废物的数量。放大结果表明，该性能得以保持，表明潜在的大规模应用。此外，合成策略显示出对多种脂族醛和酮衍生物的高效率。
• 3-METHYL-BENZOFURAN-5-OL AND ITS USE IN PERFUME COMPOSITIONS
  申请人：International Flavors & Fragrances, Inc.

  公开号：US20150111810A1

  公开（公告）日：2015-04-23

  The present invention is directed to a novel fragrance compound, 3-methyl-benzofuran-5-ol, and a method of improving, enhancing or modifying a fragrance formulation through the addition of an olfactory acceptable amount of 3-methyl-benzofuran-5-ol.

  本发明涉及一种新型香气化合物，3-甲基苯并呋喃-5-醇，以及通过添加可接受嗅觉量的3-甲基苯并呋喃-5-醇来改善、增强或修改香气配方的方法。
• 2-Substituted 3,7,8-trimethylnaphtho[1,2- b ]furan-4,5-diones as specific L-shaped NQO1-mediated redox modulators for the treatment of non-small cell lung cancer
  作者：Xiaojin Zhang、Jinlei Bian、Xiang Li、Xingsen Wu、Yanan Dong、Qidong You

  DOI：10.1016/j.ejmech.2017.06.028

  日期：2017.9

  Based on the scaffold of 3,7,8-trimethylnaphtho[1,2-b]furan-4,5-dione, a series of L-shaped derivatives with substituted side chains at the position of C2 were designed by analyzing the binding mode with NQO1. The drug-like compound 6q (named as DDO-7178) emerged as the most specific substrate of the two-electron oxidoreductase NQO1 and could hardly be reduced by one-electron oxidoreductases CPR (NQO1/CPR = 20.8). In addition, compound 6q showed much improved physicochemical properties such as water solubility than the control beta-lap. The follow-up studies indicated that 6q showed a NQO1-expressing cancer-cell-selective killing property. Preliminary mechanism studies on the anticancer effect indicated that 6q induced ROS production in an NQO1 dependent manner and activated Akt/MAPK pathways in a ROS-dependent fashion, thereby inducing apoptosis. In addition, emphasized compound 6q showed more significant antitumor efficacy than beta-lap without producing obvious toxic effects in vivo, which gave us a new tool for further investigation of NQO1-mediated redox modulators as anticancer drugs for the treatment of NQO1-overexpressed NSCLC. (C) 2017 Published by Elsevier Masson SAS.