N-((2-dimethylamino)ethyl)-7α,12α-diacetoxy-5β-cholan-24-amine-3-spiro-6'-(1',2',4',5'-tetraoxacyclohexane)-3'-spirocyclohexane | 1020072-33-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: N-((2-dimethylamino)ethyl)-7α,12α-diacetoxy-5β-cholan-24-amine-3-spiro-6'-(1',2',4',5'-tetraoxacyclohexane)-3'-spirocyclohexane
• CAS: 1020072-33-6
• 化学式: C₃₈H₆₄N₂O₈
• 分子量: 676.935
• InChiKey: LQWLGECKWNMUSC-QAUYXBRCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  48
• 可旋转键数：
  12
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  7α,12α-diacetoxy-5β-cholan-24-al-3-spiro-6'-(1',2',4',5'-tetraoxacyclohexane)-3'-spirocyclohexane 、 N,N-二甲基乙二胺 在 三乙酰氧基硼氢化钠 作用下， 以 二氯甲烷 为溶剂， 以75%的产率得到N-((2-dimethylamino)ethyl)-7α,12α-diacetoxy-5β-cholan-24-amine-3-spiro-6'-(1',2',4',5'-tetraoxacyclohexane)-3'-spirocyclohexane
  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

文献信息

• Chemical Stability of the Peroxide Bond Enables Diversified Synthesis of Potent Tetraoxane Antimalarials
  作者：Igor Opsenica、Dejan Opsenica、Kirsten S. Smith、Wilbur K. Milhous、Bogdan A. Šolaja

  DOI：10.1021/jm701417a

  日期：2008.4.1

  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.