7α,12α-diacetoxy-5β-cholan-24-amide-3-spiro-6'-(1',2',4',5'-tetraoxacyclohexane)-3'-spirocyclohexane

• 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: 7α,12α-diacetoxy-5β-cholan-24-amide-3-spiro-6'-(1',2',4',5'-tetraoxacyclohexane)-3'-spirocyclohexane
• 化学式: C₃₄H₅₃NO₉
• 分子量: 619.796
• InChiKey: ATTDEYRJQFTXHA-VKARVTOHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  44
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  133
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  7α,12α-diacetoxy-5β-cholan-24-oic acid-3-spiro-6'-(1',2',4',5'-tetraoxacyclohexane)-3'-spirocyclohexane 在 氯化铵 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 7α,12α-diacetoxy-5β-cholan-24-amide-3-spiro-6'-(1',2',4',5'-tetraoxacyclohexane)-3'-spirocyclohexane
  参考文献：
  名称：

  Mixed Steroidal 1,2,4,5-Tetraoxanes:  Antimalarial and Antimycobacterial Activity

  摘要：

  Mixed 1,2,4,5-tetraoxanes possessing simple spirocycloalkane and spirocholic acid-derived substituents were prepared and shown to have significantly higher in vitro antimalarial activity than bis-substituted tetraoxanes. Out of 41 synthesized tetraoxanes, 12 were in vitro more potent against Plasmodium falciparum chloroquine-resistant W2 clone than artemisinin, and the most potent one was 2.4 times as active as arteether. In addition, 9 compounds exhibit higher activity than chloroquine against P. falciparum chloroquine-susceptible D6 clone. Cytotoxicity was assessed for most active compounds against the Vero cell line, showing a cytotoxicity/antimalarial potency ratio of 1/(1400-9500). For the first time, tetraoxanes were screened against Mycobacterium tuberculosis with MICs as low as 4.73 muM against H37Rv strain. Mixed tetraoxanes were synthesized in a simple procedure from cholic acid methyl esters by direct coupling of steroidal gem-dihydroperoxide to simple ketones and further transformed into corresponding acids and amides.

  DOI：

  10.1021/jm020891g

文献信息

• Mixed Steroidal 1,2,4,5-Tetraoxanes:  Antimalarial and Antimycobacterial Activity
  作者：Bogdan A. Šolaja、Nataša Terzić、Gabriella Pocsfalvi、Lucia Gerena、Bernard Tinant、Dejan Opsenica、Wilbur K. Milhous

  DOI：10.1021/jm020891g

  日期：2002.8.1

  Mixed 1,2,4,5-tetraoxanes possessing simple spirocycloalkane and spirocholic acid-derived substituents were prepared and shown to have significantly higher in vitro antimalarial activity than bis-substituted tetraoxanes. Out of 41 synthesized tetraoxanes, 12 were in vitro more potent against Plasmodium falciparum chloroquine-resistant W2 clone than artemisinin, and the most potent one was 2.4 times as active as arteether. In addition, 9 compounds exhibit higher activity than chloroquine against P. falciparum chloroquine-susceptible D6 clone. Cytotoxicity was assessed for most active compounds against the Vero cell line, showing a cytotoxicity/antimalarial potency ratio of 1/(1400-9500). For the first time, tetraoxanes were screened against Mycobacterium tuberculosis with MICs as low as 4.73 muM against H37Rv strain. Mixed tetraoxanes were synthesized in a simple procedure from cholic acid methyl esters by direct coupling of steroidal gem-dihydroperoxide to simple ketones and further transformed into corresponding acids and amides.