2-hydroxy-3-(2-methyl-2-propenyl)-1,4-naphthoquinone | 127870-06-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮
• 英文名称: 2-hydroxy-3-(2-methyl-2-propenyl)-1,4-naphthoquinone
• 英文别名: 2-hydroxy-3-(2-methylallyl)-1,4-naphthoquinone；2-hydroxy-3-methallyl-[1,4]naphthoquinone；2-Hydroxy-3-methallyl-[1,4]naphthochinon
• CAS: 127870-06-8
• 化学式: C₁₄H₁₂O₃
• 分子量: 228.247
• InChiKey: KBBMTATZBHBAAQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.84
• 重原子数：
  17.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  54.37
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  2-hydroxy-3-(2-methyl-2-propenyl)-1,4-naphthoquinone 生成 2-hydroxy-3-isopropenyl-[1,4]naphthoquinone
  参考文献：
  名称：

  Cooke; Somers, Australian Journal of Scientific Research, Series A: Physical Sciences, 1950, vol. 3, p. 466,474

  摘要：

  DOI：
• 作为产物：
  描述：

  2-羟基-1,4-萘醌 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 2-hydroxy-3-(2-methyl-2-propenyl)-1,4-naphthoquinone
  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

文献信息

• Potent antitumor activity of synthetic 1,2-Naphthoquinones and 1,4-Naphthoquinones
  作者：Ngampong Kongkathip、Boonsong Kongkathip、Pongpun Siripong、Chak Sangma、Suwaporn Luangkamin、Momad Niyomdecha、Suppachai Pattanapa、Suratsawadee Piyaviriyagul、Palangpon Kongsaeree

  DOI：10.1016/s0968-0896(03)00226-8

  日期：2003.7

  Rhinacanthone (1) and two 1,2-pyranonaphthoquinones (2,3) were synthesized and found to show very potent cytotoxicity against three cancer cell lines (KB, HeLa and HepG(2)) with IC(50) values of 0.92-9.63 microM, whereas the corresponding hydroxylated derivative 4 had reduced cytotoxicity (IC(50) values of 7.61-24.13 microM). Three 1,2-furanonaphthoquinone derivatives (5-7) were also synthesized with

  合成了Rhinacanthone（1）和两个1,2-吡喃并萘醌（2,3），发现它们对三种癌细胞系（KB，HeLa和HepG（2））具有很强的细胞毒性，IC（50）值为0.92-9.63 microM，而相应的羟基化衍生物4则降低了细胞毒性（IC（50）值为7.61-24.13 microM）。还合成了三种具有与1,2-吡喃萘甲醌相似的细胞毒性的1,2-呋喃萘甲醌衍生物（5-7）。与1,2-萘醌相比，合成了与吡喃环（8-10）和呋喃环（11-13）融合的六个1,4-萘醌衍生物，它们显示出较低的细胞毒性或对癌细胞系无活性。此外，化合物13对HeLa细胞系具有明显的细胞毒性（IC（50）值为9.25 microM），而对Vero细胞无毒性。
• Non-Catalyzed Thermal Reactions of Acylquinones with Allylstannanes
  作者：Kazuhiro Maruyama、Yoshihiro Matano

  DOI：10.1246/bcsj.62.3877

  日期：1989.12

  Thermal reactions of acylquinones with allylstannanes in benzene afforded several kinds of product after column chromatography on silica gel; acyl allyl quinones, acyl allyl epoxy quinones, cyclopentanoid compounds including stannyl moiety, allyl hydroxy quinones, acyl hydroquinones, and acyl allyl hydroquinones. The main product comprises cyclopentanoid compounds, which are novel [2+3] cyclo adducts with 1,2-migration of trialkylstannyl moiety. Spectroscopic examinations (1H NMR and Vis-UV) enabled us to confirm the reaction pathways that four types of precursors were initially generated via polarized tight pair and inverted to isolated products during purification by column chromatography. Similar reactions in acetonitrile showed a remarkable difference in the reactivity, that is, acyl allyl quinones and the corresponding hydroquinones are obtained, but the [2+3] cyclo adducts are not produced at all. From 1H NMR examination, it was confirmed that three types of precursor are generated via solvent separated ion pairs at the initial stage. The rather strong reactivity of acylquinones towards allylstannanes will be due to electron withdrawing ability of acyl group.

  酰基喹诺酮与烯丙基锡在苯中的热反应经过硅胶柱层析后产生了几种产品；包括酰基烯丙基喹诺酮、酰基烯丙基环氧喹诺酮、含锡基团的环戊烷类化合物、烯丙基羟基喹诺酮、酰基羟基喹诺酮和酰基烯丙基羟基喹诺酮。主要产品是环戊烷类化合物，它们是新型的 [2+3] 环加成物，具有三烷基锡基团的 1,2-迁移。通过光谱学检查（1H NMR 和 Vis-UV），我们确认了反应途径，四种前体最初通过极化紧配对生成，并在柱层析纯化过程中转化为孤立的产品。在乙腈中的类似反应显示出明显的反应性差异，即生成酰基烯丙基喹诺酮及其对应的羟基喹诺酮，但完全不产生 [2+3] 环加成物。从 1H NMR 检查中确认，三种类型的前体在初始阶段通过溶剂分离离子对生成。酰基喹诺酮对烯丙基锡的较强反应性将是由于酰基的电子吸引能力。
• Palladium-Catalyzed Allylation of 2-Hydroxy-1,4-naphthoquinone: ­Application to the Preparation of Lapachol
  作者：Spyros Spyroudis、Georgia Kazantzi、Elizabeth Malamidou-Xenikaki

  DOI：10.1055/s-2007-967947

  日期：2007.2

  The Pd(PPh3)4-catalyzed reaction of 2-hydroxy-1,4-naphthoquinone (lawsone) with allyl alcohols and allyl esters offers an easy access to 3-allyl-2-hydroxy-1,4-naphthoquinones, compounds with interesting biological activity. The reaction finds application in the preparation of lapachol. Other 2-hydroxy-1,4-benzoquinones give allylation products in low yields.

  Pd(PPh3)4催化的2-羟基-1,4-萘醌（lawsone）与烯丙醇和烯丙基酯的反应为合成3-烯丙基-2-羟基-1,4-萘醌提供了一种简单的方法，这些化合物具有有趣的生物活性。该反应在拉帕克醇的制备中具有应用价值。其他2-羟基-1,4-苯醌的反应产物产率较低。
• WO2008/66299
  申请人：——

  公开号：——

  公开（公告）日：——
• Synthesis and evaluation of (±)-dunnione and its ortho-quinone analogues as substrates for NAD(P)H:quinone oxidoreductase 1 (NQO1)
  作者：Jinlei Bian、Lili Xu、Bang Deng、Xue Qian、Jun Fan、Xiuwen Yang、Fang Liu、Xiaoli Xu、Xiaoke Guo、Xiang Li、Haopeng Sun、Qidong You、Xiaojin Zhang

  DOI：10.1016/j.bmcl.2015.01.057

  日期：2015.3

  Natural product (+/-)-dunnione (2) and its ortho-quinone analogues (3-8) were synthesized and found to be substrates for NQO1. The structure-activity relationship study revealed that the biological activity was favored by the presence of methyl group at the C ring and methoxy group at the A ring. The docking studies supported the rationalization of the metabolic studies. Deeper location in the active site of NQO1, interactions with hydrophobic pocket and C-H center dot center dot center dot pi interactions with the adjacent Phe178 residue contributed to the better catalytic efficiency and specificity to NQO1. Cytotoxicity studies and determination of superoxide (O-2(center dot)) production in the presence and absence of the NOQ1 inhibitor dicoumarol confirmed that the ortho-quinones exerted their antitumor activity through NQO1-mediated ROS production by redox cycling. (C) 2015 Elsevier Ltd. All rights reserved.