2,5-dihydroxy-3-(3-methylbut-2-enyl)naphthalene-1,4-dione

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 2,5-dihydroxy-3-(3-methylbut-2-enyl)naphthalene-1,4-dione
• 英文别名: 5-hydroxylapachol；hydroxylapachol
• 化学式: C₁₅H₁₄O₄
• 分子量: 258.274
• InChiKey: XOFJIZXNAOYRAW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.94
• 重原子数：
  19.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  74.6
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2,5-dihydroxy-3-(3-methylbut-2-enyl)naphthalene-1,4-dione 在 硫酸 作用下， 以97%的产率得到6-hydroxy-α-lapachone
  参考文献：
  名称：

  合成萘醌与拉帕胆有关的抗增殖活性。首次合成5-羟基小a酚

  摘要：

  从juglone（6）合成了一系列5-hydroxy-1,4-naphthoquinones类似物，并研究了它们对代表6种人类实体瘤细胞系的抗增殖活性。2,5-二羟基-3-（3-甲基丁-2-烯基）萘-1,4-二酮（4）和2,3-二氢-5-羟基-2-（丙-1-烯-2- yl）naphtho [2,3 - b ] furan-4,9-dione（27）是最有效的抗增殖剂，其GI 50值分别为0.42-8.1和0.80-2.2μM。结果为5-羟基萘醌的某些结构性质与其抗增殖活性之间的相关性提供了见识。

  DOI：

  10.1016/j.bmc.2010.02.032
• 作为产物：
  描述：

  1,5-二羟基萘 在 吡啶 、 aluminum (III) chloride 、 N-氯代丁二酰亚胺 、 lithium hydride 、 potassium carbonate 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 、 溶剂黄146 、 二甲基亚砜 为溶剂， 反应 28.17h， 生成 2-(3-methylbut-2-enyloxy)-5-hydroxynaphthalene-1,4-dione 、 2,5-dihydroxy-3-(2-methylbut-3-en-2-yl)naphthalene-1,4-dione 、 2,5-dihydroxy-3-(3-methylbut-2-enyl)naphthalene-1,4-dione
  参考文献：
  名称：

  小萘醌文库的合成和细胞毒活性：胡桃素的首次合成

  摘要：

  已设计合成方案来合成 grecoketidone (2k)、5-hydroxylapachol (2g) 和最近发现的天然产物胡桃苷 (2o) 及其衍生物，从而形成不同 1,4-萘醌的小型库，目的是寻找新的活性化合物。在我们的系列中，2-O-烷基化萘醌在侧链中具有酯官能团且在 C-5 处具有游离 OH 基团，表现出最佳活性。化合物 2f、2m 和 2n 在较低微摩尔范围内对 12 种肿瘤细胞系显示出 GI50 值，而胡桃苷 (2o) 显示出对糖原合酶激酶 3β 的显着有效抑制，IC50 值为 2.03 μM。此外，还对最活跃的细胞毒性化合物的作用方式进行了研究。据我们所知，

  DOI：

  10.1002/ejoc.201402272

文献信息

• β-Lapachone analogs with enhanced antiproliferative activity
  作者：Carla Ríos-Luci、Evelyn L. Bonifazi、Leticia G. León、Juan C. Montero、Gerardo Burton、Atanasio Pandiella、Rosana I. Misico、José M. Padrón

  DOI：10.1016/j.ejmech.2012.04.008

  日期：2012.7

  In this study, we describe the synthesis of a series of alpha- and beta-lapachone containing hydroxyl or methoxyl groups on the benzene ring, by means of the selective acid promoted cyclization of the appropriate lapachol analog. The evaluation of the antiproliferative activity in human solid tumor cell lines provided 7-hydroxy-beta-lapachone as lead with enhanced activity over the parent drug beta-lapachone. Cell cycle studies, protein expression experiments, and reactive oxygen species analysis revealed that, similarly to beta-lapachone, ROS formation and DNA damage are critical factors in the cellular toxicity of 7-hydroxy-beta-lapachone. (C) 2012 Elsevier Masson SAS. All rights reserved.
• QSAR on antiproliferative naphthoquinones based on a conformation-independent approach
  作者：Pablo R. Duchowicz、Daniel O. Bennardi、Daniel E. Bacelo、Evelyn L. Bonifazi、Carla Rios-Luci、José M. Padrón、Gerardo Burton、Rosana I. Misico

  DOI：10.1016/j.ejmech.2014.02.057

  日期：2014.4

  The antiproliferative activities of a series of 36 naphthoquinone derivatives were subjected to a Quantitative Structure Activity Relationships (QSAR) study. For this purpose a panel of four human cancer cell lines was used, namely HBL-100 (breast), HeLa (cervix), SW-1573 (non-small cell lung) and WiDr (colon). A conformation-independent representation of the chemical structure was established in order to avoid leading with the scarce experimental information on X-ray crystal structure of the drug interaction. The 1179 theoretical descriptors derived with E-Dragon and Recon software were simultaneously analyzed through linear regression models based on the Replacement Method variable subset selection technique. The established models were validated and tested through the use of external test sets of compounds, the Leave-One-Out Cross Validation method, Y-Randomization and Applicability Domain analysis. (c) 2014 Elsevier Masson SAS. All rights reserved.
• Antiproliferative activity of synthetic naphthoquinones related to lapachol. First synthesis of 5-hydroxylapachol
  作者：Evelyn L. Bonifazi、Carla Ríos-Luci、Leticia G. León、Gerardo Burton、José M. Padrón、Rosana I. Misico

  DOI：10.1016/j.bmc.2010.02.032

  日期：2010.4

  A series of 5-hydroxy-1,4-naphthoquinones analogues was synthesized from juglone (6) and their antiproliferative activity against a representative panel of six human solid tumor cell lines has been investigated. The 2,5-dihydroxy-3-(3-methylbut-2-enyl)naphthalene-1,4-dione (4) and 2,3-dihydro-5-hydroxy-2-(prop-1-en-2-yl)naphtho[2,3-b]furan-4,9-dione (27) were the most potent antiproliferative agents

  从juglone（6）合成了一系列5-hydroxy-1,4-naphthoquinones类似物，并研究了它们对代表6种人类实体瘤细胞系的抗增殖活性。2,5-二羟基-3-（3-甲基丁-2-烯基）萘-1,4-二酮（4）和2,3-二氢-5-羟基-2-（丙-1-烯-2- yl）naphtho [2,3 - b ] furan-4,9-dione（27）是最有效的抗增殖剂，其GI 50值分别为0.42-8.1和0.80-2.2μM。结果为5-羟基萘醌的某些结构性质与其抗增殖活性之间的相关性提供了见识。
• Synthesis and Cytotoxic Activity of a Small Naphthoquinone Library: First Synthesis of Juglonbutin
  作者：Elke Brötz、Jennifer Herrmann、Jutta Wiese、Heidi Zinecker、Armin Maier、Gerhardt Kelter、Johannes F. Imhoff、Rolf Müller、Thomas Paululat

  DOI：10.1002/ejoc.201402272

  日期：2014.8

  products juglonbutin (2o) and its derivatives, leading to a small library of different 1,4-naphthoquinones with the intention of finding new active compounds. Within our collection, 2-O-alkylated naphthoquinones with an ester functionality in the side-chain and a free OH group at C-5 showed the best activities. Compounds 2f, 2m, and 2n showed GI50 values against 12 tumor cell lines in the lower micromolar

  已设计合成方案来合成 grecoketidone (2k)、5-hydroxylapachol (2g) 和最近发现的天然产物胡桃苷 (2o) 及其衍生物，从而形成不同 1,4-萘醌的小型库，目的是寻找新的活性化合物。在我们的系列中，2-O-烷基化萘醌在侧链中具有酯官能团且在 C-5 处具有游离 OH 基团，表现出最佳活性。化合物 2f、2m 和 2n 在较低微摩尔范围内对 12 种肿瘤细胞系显示出 GI50 值，而胡桃苷 (2o) 显示出对糖原合酶激酶 3β 的显着有效抑制，IC50 值为 2.03 μM。此外，还对最活跃的细胞毒性化合物的作用方式进行了研究。据我们所知，