7-hydroxy-2,2-dimethyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione | 22333-59-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 萘并吡喃类
• 英文名称: 7-hydroxy-2,2-dimethyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione
• 英文别名: 7-Hydroxy-beta-lapachone；7-hydroxy-2,2-dimethyl-3,4-dihydrobenzo[h]chromene-5,6-dione
• CAS: 22333-59-1
• 化学式: C₁₅H₁₄O₄
• 分子量: 258.274
• InChiKey: LLHZGJVLXANLBF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7-hydroxy-2,2-dimethyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione 、 三甲基乙酰氯 在 2,2-二羟甲基丙酸 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以40%的产率得到3,4,5,6-tetrahydro-2,2-dimethyl-5,6-dioxo-2H-benzo[h]chromen-7-yl pivalate
  参考文献：
  名称：

  β-Lapachone analogs with enhanced antiproliferative activity

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2012.04.008
• 作为产物：
  描述：

  3,5-dihydroxy-2-(3-methylbut-2-en-1-yl)naphthalene-1,4-dione 在 甲烷磺酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以51%的产率得到7-hydroxy-2,2-dimethyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione
  参考文献：
  名称：

  Concise Synthesis and Evaluation of ortho-Naphthoquinones Containing a Phenolic Hydroxy Moiety

  摘要：

  A concise and efficient synthesis method for the preparation of antiproliferative ortho-naphthoquinones is described. Notably, the synthesis of ortho-furanonaphthoquinone was achieved by utilizing a regioselective oxidative conjugate addition of dimethylamine and the Sonogashira coupling/cyclization reaction as the key steps. Additionally, an improved synthesis of hydroxy-P-lapachone was established and included a regioselective prenylation by directed ortho-lithiation. In vitro antiproliferative effects of the synthesized against a panel of 39 human cancer cell lines were evaluated and the results were directly compared to those previously obtained for 1.

  DOI：

  10.3987/com-20-14219

文献信息

• Synthesis of new 9-hydroxy-α- and 7-hydroxy-β-pyran naphthoquinones and cytotoxicity against cancer cell lines
  作者：David R. da Rocha、Ana C. G. de Souza、Jackson A. L. C. Resende、Wilson C. Santos、Evelyne A. dos Santos、Cláudia Pessoa、Manoel O. de Moraes、Letícia V. Costa-Lotufo、Raquel C. Montenegro、Vitor F. Ferreira

  DOI：10.1039/c1ob05209h

  日期：——

  A synthetic method to obtain α- and β-pyran naphthoquinones 10 and 11 with a hydroxyl substituent on the aromatic ring was developed. Two series of α- and β-pyran naphthoquinones were obtained from the 8-hydroxy-lawsone, and their anticancer properties were evaluated against four tumor cell lines. In general, the new compounds displayed good activity, possibly indicating that these compounds have increased pro-oxidant capacity. The 9-hydroxy-α-lapachone and 7-hydroxy-β-lapachone analogues of the natural products α-lapachone and β-lapachone were successfully produced by this methodology.

  研究人员开发了一种合成方法，以获得芳香环上具有羟基取代基的δ-和δ-吡喃萘醌10和11。从 8-hydroxy-lawsone 中得到了两个系列的 α- 和 β-pyran 萘醌，并评估了它们对四种肿瘤细胞系的抗癌特性。总的来说，新化合物显示出良好的活性，这可能表明这些化合物具有更强的抗氧化能力。用这种方法成功地制备了天然产物δ-拉帕醌和δ-拉帕醌的9-羟基-δ-拉帕醌和7-羟基-δ-拉帕醌类似物。
• Two New Syntheses of the Pyranojuglone Pigment ?-Caryopterone
  作者：Takeshi Matsumoto、Akitami Ichihara、Mitsutoshi Yanagiya、Tamio Yuzawa、Akiyoshi Sannai、Hideaki Oikawa、Sadao Sakamura、Conrad Hans Eugster

  DOI：10.1002/hlca.19850680827

  日期：1985.12.18

  process, 3-methoxyjuglone (= 8-hydroxy-2-methoxy-1,4-naphthoquinone; 9) has been synthesized from 1,2,4-trimethoxybenzene (5) and converted, after prenylation, to α-caryopterone (1; Scheme 1), a pyranojuglone pigment from Caryopteris clandonensis. On the other hand, juglone (= 5-hydroxy-1,4-naphthoquinone; 12) was regioselectively prenylated at C(2) via its 1-methoxy-cyclohexa-1,3-diene adduct 15(Scheme

  通过一个简单的方法，由1,2,4-三甲氧基苯（5）合成了3-甲氧基juglone（= 8-羟基-2-甲氧基-1,4-萘醌; 9），并在异戊二烯化后转化为α-环戊烯酮（1；方案1），来自Caryopteris clandonensis的吡喃juglone颜料。另一方面，通过其1-甲氧基-环己-1,3-二烯加合物15 （方案2），在C（2）上对juglone（= 5-hydroxy-1,4-naphthoquinone; 12）进行区域选择性炔丙基化。如此形成的2-异戊烯基胡克隆酮（4）在氧化和其他反应后导致1。
• Effect of 9-hydroxy-α- and 7-hydroxy-β-pyran Naphthoquinones on Trypanosoma cruzi and Structure-activity Relationship Studies
  作者：David Rochaa、Alessandra Souza、Ana Souza、Helena Castro、Carlos Rodrigues、Rubem Menna-Barreto、Solange Castro、Vitor Ferreira

  DOI：10.2174/1573406410666131229151303

  日期：2014.8.4

  The available treatment for the prevention and cure of Chagas disease, caused by the protozoan Trypanosoma cruzi, is still unsatisfactory. Thus, there is an urgent need to develop new drugs. In the last few years, our research group has focused on finding a new chemical entity able to target the infectious bloodstream trypomastigotes. In this study, we assayed 16 β-lapachone analogous with modifications in the pyran and aromatic ring to find a new prototype with high trypanocidal activity. Interestingly, two ortho-naphthoquinones presented the best trypanocidal profile (8c and 8d with an IC50/24 h of 26.9 ± 1.3 and 23.5 ± 2.5 μM, respectively), which were 4 to 17 times more effective than β-lapachone (391.5 ± 16.5 μM) and the standard drug benznidazole (103.6 ± 0.6 μM). The introduction of a hydroxyl group on the compounds’ aromatic ring modulated their biological profile by increasing their activity not only for cancer cells (MDAMB435), as previously described in literature, but also against T. cruzi. The Structure-Activity Relationship (SAR) study indicated that this introduction modulated HOMO and MEP parameters, improving the trypanocidal activity.

  预防和治疗由原生动物锥虫引起的恰加斯病的可用治疗方法 克鲁兹，仍然不满意。因此，迫切需要开发新药。近几年来，我们课题组 专注于寻找一种能够针对传染性血流锥鞭毛体的新化学实体。在这项研究中，我们 分析了 16 β-lapachone 类似物，并在吡喃和芳环上进行了修饰，以找到具有高 杀锥虫活性。有趣的是，两种邻萘醌具有最佳的杀锥虫特性（8c 和 8d IC50/24 h 分别为 26.9 ± 1.3 和 23.5 ± 2.5 μM），比 β-拉帕酮（391.5 ± 16.5 μM) 和标准药物苯并硝唑 (103.6 ± 0.6 μM)。在其上引入羟基 化合物的芳香环不仅通过增加癌细胞的活性来调节其生物学特征（MDAMB435）， 正如之前文献中所描述的，但也针对 T. cruzi。构效关系 (SAR) 研究 表明这种引入调节了 HOMO 和 MEP 参数，提高了杀锥虫活性。
• Synthesis of dehydro-α-lapachones, α- and β-lapachones, and screening against cancer cell lines
  作者：Caroline dos S. Moreira、Caroline D. Nicoletti、Daniel P. Pinheiro、Leonardo G. C. de Moraes、Debora O. Futuro、Vitor F. Ferreira、Claudia do Ó Pessoa、David R. da Rocha

  DOI：10.1007/s00044-019-02439-w

  日期：2019.12

  14 new naphthoquinones were prepared and tested against human cancer cell lines PC-3 (prostate), HCT-116 (colon carcinoma), SNB-19 (glioblastoma), HL-60 (leukemia) and MCF-7 (breast), and a nontumor cell line L929 (murine fibroblasts) to determine cytotoxicity with the MTT assay. 8-OH-beta -lapachones (14a, 14c, 14d) presented best results, showing low IC50 values and high selectivity for HCT-116 and HL-60 tumor cells.
• Synthetic methods for the preparation of ARQ 501 (β-Lapachone) human blood metabolites
  作者：Rui-Yang Yang、Darin Kizer、Hui Wu、Erika Volckova、Xiu-Sheng Miao、Syed M. Ali、Manish Tandon、Ronald E. Savage、Thomas C.K. Chan、Mark A. Ashwell

  DOI：10.1016/j.bmc.2008.03.073

  日期：2008.5

  ARQ 501 (3,4-dihydro-2,2-dimethyl-2H-naphthol[1,2-b]pyran-5,6-dione), a synthetic version of beta-Lapachone, is a promising anti-cancer agent currently in multiple Phase II clinical trials. Promising anti-cancer activity was observed in Phase I and Phase II trials. Metabolism by red blood cells of drugs is an understudied area of research and the metabolites arising from oxidative ring opening (M2 and M3), decarbonylation/ ring contraction (M5), and decarbonylation/ oxidation (M4 and M6) of ARQ 501 offer a unique opportunity to provide insight into these metabolic processes. Since these metabolites were not detected in in vitro incubations of ARQ 501 with liver microsomes and were structurally diverse, confirmation by chemical synthesis was considered essential. In this report, we disclose the synthetic routes employed and the characterization of the reference standards for these blood metabolites as well as additional postulated structures, which were not confirmed as metabolites. (C) 2008 Elsevier Ltd. All rights reserved.