7,8,15,16-tetraoxa-dispiro[5.2.5.2]hexadecane-3-carboxylic acid | 859161-50-5

• 分子结构分类: 有机化合物 - 有机氧化合物 - 有机氧化物
• 英文名称: 7,8,15,16-tetraoxa-dispiro[5.2.5.2]hexadecane-3-carboxylic acid
• 英文别名: 7,8,15,16-tetraoxadispiro_[5.2.59.26]hexadecane-3-carboxylic acid；7,8,15,16-Tetraoxadispiro[5.2.5~9~.2~6~]hexadecane-3-carboxylic acid；7,8,15,16-tetraoxadispiro[5.2.59.26]hexadecane-12-carboxylic acid
• CAS: 859161-50-5
• 化学式: C₁₃H₂₀O₆
• 分子量: 272.298
• InChiKey: IGQPZGPAYLDOJR-UHFFFAOYSA-N

物化性质

• 沸点：
  400.3±45.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  74.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  7,8,15,16-tetraoxa-dispiro[5.2.5.2]hexadecane-3-carboxylic acid 在 氯甲酸乙酯 、 三乙胺 、 氯化铵 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以80%的产率得到7,8,15,16-Tetraoxadispiro[5.2.59.26]hexadecane-12-carboxamide
  参考文献：
  名称：

  Chemical Stability of the Peroxide Bond Enables Diversified Synthesis of Potent Tetraoxane Antimalarials

  摘要：

  The development of widespread drug resistance to chloroquine (CQ(a)) has resulted in severe health issues for countries in malaria endemic regions. The antimalarial properties of artemisinin 2 and of other peroxides, such as 1,2,4,5-tetraoxacy-cloalkanes (tetraoxanes), have recently begun to be exploited in the development of new approaches to fighting CQ-resistant strains of malaria. New tetraoxanes employing a steroidal backbone have now been prepared that are highly active, are inexpensive, and demonstrate low toXieity.(5,6) A part of our research in this field is focused on the development of a new type of tetraoxane with nonidentical substituents(6) that utilize a steroid and small cyclohexylidene carriers possessing secondary amide bonds. Also, during our work in this field we discovered that tetraoxanes are unusually stable, even. at pH 1.6,(6c) a characteristic that subsequently allowed the synthesis of many interesting derivatives. This communication encompasses the synthesis of various amino-functionalized antimalarials based on the appreciable stability of the tetraoxane moiety to reaction conditions such as reductive amination and LiAlH4 reduction. Their respective antimalarial activities and the pronounced antiproliferative activity of certain products are reported along with in vitro metabolism studies.

  DOI：

  10.1021/jm701417a
• 作为产物：
  描述：

  Ethyl 7,8,15,16-tetraoxadispiro[5.2.59.26]hexadecane-12-carboxylate 在 氢氧化钾 、 水 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以85%的产率得到7,8,15,16-tetraoxa-dispiro[5.2.5.2]hexadecane-3-carboxylic acid
  参考文献：
  名称：

  Design and synthesis of orally active dispiro 1,2,4,5-tetraoxanes; synthetic antimalarials with superior activity to artemisinin

  摘要：

  非对称结构的二环缩酮和螺环四氧戊环通过酸催化下的双氢过氧化物与酮的环化缩合反应设计合成。通过还原胺化反应和酰胺键形成，引入水溶性和极性功能基团，产生了几种体外抗疟活性低至纳摩尔级别的类似物。这类环氧过氧化物药物的若干类似物表现出了前所未有的口服抗疟活性水平。

  DOI：

  10.1039/b613565j

文献信息

• Anti-Mycobacterial Peroxides: A New Class of Agents for Development Against Tuberculosis
  作者：Christiaan W. van der Westhuyzen、Richard K. Haynes、Jenny-Lee Panayides、Ian Wiid、Christopher J. Parkinson

  DOI：10.2174/1573406415666190430143535

  日期：2020.4.17

  preferably, a tetraoxane peroxidic structure results in antitubercular activity in vitro. The same effect is not observed in the absence of the pyrimidine or with other heteroaromatic substituents. CONCLUSION The incorporation of a pyrimidinyl residue adjacent to the peroxidic function in an organic peroxide results in anti-tubercular activity in an otherwise inactive peroxidic compound. This will be

  背景技术除少数例外，许多年前开发了现有的结核病药物，并且耐药性出现了。这产生了对具有离散作用方式的新药的需求。有证据表明，结核病（像其他细菌一样）易受氧化压力的影响，尚需以与已证明在疟疾治疗中非常成功的相似方法适当地用作治疗方法。目的开发一种结合细菌铁载体的替代方法，该方法可产生抗结核性过氧化铅，随后可作为抗结核的新药开发。方法制备了8种新型过氧化物，并将其抗结核活性（H37Rv）与现有青蒿素衍生物进行了体外比较。评估了针对L6大鼠骨骼肌成肌细胞和HeLa宫颈癌细胞系的潜在毒性。结果向青蒿素或优选四恶烷过氧化物结构中添加嘧啶基残基可导致体外抗结核活性。在不存在嘧啶或具有其他杂芳族取代基的情况下，未观察到相同的效果。结论在有机过氧化物中，与过氧化功能相邻的嘧啶基残基的引入会导致原本没有活性的过氧化化合物具有抗结核活性。这将是创建针对肺结核的氧化药物的有用方法。四恶烷过氧化物的结构在体外具有抗
• Mild Functionalization of Tetraoxane Derivatives via Olefin Metathesis: Compatibility of Ruthenium Alkylidene Catalysts with Peroxides
  作者：Anupam Jana、Karol Grela

  DOI：10.1021/acs.orglett.6b03688

  日期：2017.2.3

  An easy and mild functionalization method of tetraoxane derivatives via olefin metathesis is reported. This reaction offers a new method to afford fully functionalized tetraoxanes in high yields. This method is also utilized in the functionalization of bioactive compounds.

  报道了一种通过烯烃易位的四恶烷衍生物的简便温和的官能化方法。该反应提供了一种以高收率提供完全官能化的四恶烷的新方法。该方法还用于生物活性化合物的功能化。
• Novel conjugates of endoperoxide and 4-anilinoquinazoline as potential anticancer agents
  作者：Jing Yang、Zhengchao Tu、Xin Xu、Jinfeng Luo、Xing Yan、Chongzhao Ran、Xinliang Mao、Ke Ding、Chunhua Qiao

  DOI：10.1016/j.bmcl.2017.02.023

  日期：2017.3

  In the present study, endoperoxide and 4-anilinognazoline were conjugated to obtain a series of compounds. These conjugates exhibited high antiproliferative potency against a number of cancer cell lines, including the epidermal growth factor receptor (EGFR) L858R/T790M mutant cell. Compound 5 was selected as a representative for mechanistic study. Further experiments revealed the conjugate's reactive oxygen species (ROS) generating ability, apoptosis inducing activity and involvement in EGFR downstream signaling pathways. (C) 2017 Elsevier Ltd. All rights reserved.
• New Chimeric Antimalarials with 4-Aminoquinoline Moiety Linked to a Tetraoxane Skeleton
  作者：Igor Opsenica、Dejan Opsenica、Charlotte Anne Lanteri、Lalaine Anova、Wilbur K. Milhous、Kirsten S. Smith、Bogdan A. Šolaja

  DOI：10.1021/jm8006905

  日期：2008.10.9

  The synthesis of the chimeric molecules consisting of two pharmacophores, tetraoxane and 7-chloro-4-aminoquinoline, is reported. The tetraoxanes 2, 4, and 8 show relatively potent in vitro antimalarial activities, with IC90 values for the Plasmodium falciparum strain W2 of 2.26, 12.44, and 10.74 nM, respectively. In addition, two compounds, 2 and 4, cured mice in a modified Thompson test for antimalarial blood stage activity, with a minimum curative dose of 80 mg/kg, a minimum active dose of 20 mg/kg/day, and a maximum tolerated dose of > 960 mg/kg.
• Praziquantel derivatives exhibit activity against both juvenile and adult Schistosoma japonicum
  作者：Wen-wen Duan、Si-jie Qiu、Yue Zhao、Huan Sun、Chunhua Qiao、Chao-ming Xia

  DOI：10.1016/j.bmcl.2011.12.133

  日期：2012.2

  A praziquantel analog 10-hydroxy praziquantel and eight praziquantel/peroxide conjugates were synthesized. The biological activity of these compounds was evaluated against juvenile and adult stages of Schistosoma japonicum. Unlike praziquantel, 10-hydroxy praziquantel exhibits activity against both juvenile and adult Schistosoma japonicumin. All hybrid compounds displayed modest to significant worm killing activity. The present study has important significance for the development of hybrid antischistosomal drugs. Crown Copyright (C) 2012 Published by Elsevier Ltd. All rights reserved.