7,14,15-Trioxadispiro<5.1.5.2>pentadecan | 129731-36-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三氧戊环
• 英文名称: 7,14,15-Trioxadispiro<5.1.5.2>pentadecan
• 英文别名: 7,14,15-Trioxadispiro[5.1.5.2]pentadecane；7,14,15-trioxadispiro[5.1.58.26]pentadecane
• CAS: 129731-36-8
• 化学式: C₁₂H₂₀O₃
• 分子量: 212.289
• InChiKey: FZAKEAZCMNLJDB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  27.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7,14,15-Trioxadispiro<5.1.5.2>pentadecan 在 三氟甲磺酸三甲基硅酯 作用下， 以50%的产率得到6-己内酯
  参考文献：
  名称：

  Selectivity in Lewis acid-mediated fragmentations of peroxides and ozonides: application to the synthesis of alkenes, homoallyl ethers, and 1,2-dioxolanes †

  摘要：

  二烷基过氧化物和臭氧化物的断裂强烈受到路易斯酸选择的影响。TiCl4促进叔过氧化物的C-O离子化（SN1反应），而SnCl4和BF3·OEt2促进O-O异裂（Hock反应）。阳离子中间体被烯丙基三甲基硅烷捕获，得到烯丙基化的烷烃和同烯丙基醚。在缺少亲核试剂的情况下，臭氧化物（1,2,4-三氧杂环戊烷）不可避免地发生O-O异裂。然而，烯丙基三甲基硅烷和SnCl4的组合导致通过捕获SN1离子化产生的中等体形成1,2-二氧杂环戊烷。

  DOI：

  10.1039/b001391i
• 作为产物：
  描述：

  环己酮O-甲基肟 在 ozone 作用下， 以 环己酮 、 Petroleum ether 、 正戊烷 为溶剂， 生成 7,14,15-Trioxadispiro<5.1.5.2>pentadecan
  参考文献：
  名称：

  Spiro and dispiro 1,2,4-trioxolane antimalarials

  摘要：

  描述了一种利用螺环或二螺环1,2,4-三噁烷治疗疟疾的方法和手段。首选的1,2,4-三噁烷包括在三噁烷基团的一侧具有螺环戊烷基团，并在三噁烷基团的另一侧具有螺环环己基或螺环哌啶基团，其中螺环环己基环在4-位功能化或取代，或者螺环哌啶基团在氮原子处功能化或取代。与青蒿素半合成衍生物相比，本发明的化合物结构简单，易于合成，无毒，并且对疟原虫具有强效作用。

  公开号：

  US06486199B1

文献信息

• [EN] 1,2,4-TRIOXOLANE ANTIMALARIALS<br/>[FR] ANTIPALUDIQUES A BASE DE 1,2,4-TRIOXOLANE
  申请人：MEDICINES MALARIA VENTURE MMV

  公开号：WO2003000676A1

  公开（公告）日：2003-01-03

  A means and method for treating malaria, schistosomiasis, and cancer using a spiro or dispiro 1,2,4-trioxolane is described. The preferred 1,2,4-trioxolanes include a spiroadamantane group on one side of the trioxolane group, and a spirocyclohexyl on the other side of the trioxolane group, whereby the spirocyclohexyl ring is preferably substituted at the 4-position. In comparison to artemisinin semisynthetic derivatives, the compounds of this invention are structurally simple, easy to synthesize, non-toxic, and potent against malarial parasites.

  本发明涉及使用螺环或双螺环1,2,4-三噁烷治疗疟疾、血吸虫病和癌症的方法和手段。首选的1,2,4-三噁烷包括一个螺环戊烷基团位于三噁烷基团的一侧，以及一个螺环己基位于三噁烷基团的另一侧，其中螺环己环在4位处优选被取代。与青蒿素半合成衍生物相比，本发明的化合物结构简单，易于合成，无毒，并且对疟原虫具有很强的杀灭作用。
• SPIRO AND DISPIRO 1,2,4-TRIOXOLANE ANTIMALARIALS
  申请人：VENNERSTROM JONATHAN L.

  公开号：US20080125441A1

  公开（公告）日：2008-05-29

  A means and method for treating malaria, schistosomiasis, and cancer using a Spiro or dispiro 1,2,4-trioxolane is described. The preferred 1,2,4-trioxolanes include a spiroadamantane group on one side of the trioxolane group, and a spirocyclohexyl on the other side of the trioxolane group, whereby the spirocyclohexyl ring is preferably substituted at the 4-position. In comparison to artemisinin semisynthetic derivatives, the compounds of this invention are structurally simple, easy to synthesize, non-toxic, and potent against malarial parasites.

  本发明涉及使用Spiro或dispiro 1,2,4-三噁烷治疗疟疾、血吸虫病和癌症的方法和手段。首选的1,2,4-三噁烷包括一个spiroadamantane基团位于三噁烷基团的一侧，而spirocyclohexyl位于三噁烷基团的另一侧，其中spirocyclohexyl环在4位处被取代。与青蒿素半合成衍生物相比，本发明化合物结构简单，易于合成，无毒，并且对疟原虫具有强效作用。
• DISPIRO 1,2,4-TRIOXOLANE ANTIMALARIALS
  申请人：VENNERSTROM JONATHAN L.

  公开号：US20080125411A1

  公开（公告）日：2008-05-29

  A means and method for treating malaria, schistosomiasis, and cancer using a spiro or dispiro 1,2,4-trioxolane is described. The preferred 1,2,4-trioxolanes include a spiroadamantane group on one side of the trioxolane group, and a spirocyclohexyl on the other side of the trioxolane group. In comparison to artemisinin semisynthetic derivatives, the compounds of this invention are structurally simple, easy to synthesize, non-toxic, and potent against malarial parasites. The compounds of the invention unexpectedly provide a single-dose cure for malaria, as well as prophylactic activity against the same. The compounds are also active against schistosomiasis and cancer.

  本发明提供了一种治疗疟疾、血吸虫病和癌症的方法和手段，使用螺环或二螺环1,2,4-三噁烷酮。首选的1,2,4-三噁烷酮包括一个螺环戊烷基团在三噁烷基团的一侧，以及一个螺环己基在三噁烷基团的另一侧。与青蒿素半合成衍生物相比，本发明的化合物结构简单，易于合成，无毒，并且对疟原虫具有强效作用。该发明的化合物意外地提供了一次性治愈疟疾的方法，以及对其的预防活性。该化合物也对血吸虫病和癌症具有活性。
• Griesbaum, Karl; Krieger-Beck, Petra; Beck, Johannes, Chemische Berichte, 1991, vol. 124, # 2, p. 391 - 396
  作者：Griesbaum, Karl、Krieger-Beck, Petra、Beck, Johannes

  DOI：——

  日期：——
• Spiro and Dispiro-1,2,4-trioxolanes as Antimalarial Peroxides:  Charting a Workable Structure−Activity Relationship Using Simple Prototypes
  作者：Yuxiang Dong、Jacques Chollet、Hugues Matile、Susan A. Charman、Francis C. K. Chiu、William N. Charman、Bernard Scorneaux、Heinrich Urwyler、Josefina Santo Tomas、Christian Scheurer、Christopher Snyder、Arnulf Dorn、Xiaofang Wang、Jean M. Karle、Yuanqing Tang、Sergio Wittlin、Reto Brun、Jonathan L. Vennerstrom

  DOI：10.1021/jm049040u

  日期：2005.7.1

  This paper describes the discovery of synthetic 1,2,4-trioxolane antimalarials and how we established a workable structure-activity relationship in the context of physicochemical, biopharmaceutical, and toxicological profiling. An achiral dispiro-1,2,4-trioxolane (3) in which the trioxolane is flanked by a spiroadamantane and spirocyclohexane was rapidly identified as a lead compound. Nonperoxidic 1,3-dioxolane isosteres of 3 were inactive as were trioxolanes without the spiroadamantane. The trioxolanes were substantially less effective in a standard oral suspension formulation compared to a solubilizing formulation and were more active when administered subcutaneously than orally, both of which suggest substantial biopharmaceutical liabilities. Nonetheless, despite their limited oral bioavailability, the more lipophilic trioxolanes generally had better oral activity than their more polar counterparts. In pharmacokinetic experiments, four trioxolanes had high plasma clearance values, suggesting a potential metabolic instability. The toxicological profiles of two trioxolanes were comparable to that of artesunate.