(+)-octahydro-3,6α-dimethyl-3,12-epoxy-9β-(3'-(trifluoromethyl)propyl)-12H-pyrano[4,3j]-1,2-benzodioxepin-10(3H)-one | 467224-02-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (+)-octahydro-3,6α-dimethyl-3,12-epoxy-9β-(3'-(trifluoromethyl)propyl)-12H-pyrano[4,3j]-1,2-benzodioxepin-10(3H)-one
• 英文别名: (1R,4S,5R,8S,9R,12S,13R)-1,5-dimethyl-9-(4,4,4-trifluorobutyl)-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-one
• CAS: 467224-02-8
• 化学式: C₁₈H₂₅F₃O₅
• 分子量: 378.389
• InChiKey: PLQRQNZEPLAUHQ-JNFWJAKCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (+)-octahydro-3,6α-dimethyl-3,12-epoxy-9β-(3'-(trifluoromethyl)propyl)-12H-pyrano[4,3j]-1,2-benzodioxepin-10(3H)-one 在 二异丁基氢化铝 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以100%的产率得到(1R,4S,5R,8S,9R,12R,13R)-1,5-dimethyl-9-(4,4,4-trifluorobutyl)-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-ol
  参考文献：
  名称：

  Structure−Activity Relationships of the Antimalarial Agent Artemisinin. 7. Direct Modification of (+)-Artemisinin and In Vivo Antimalarial Screening of New, Potential Preclinical Antimalarial Candidates

  摘要：

  On the basis of earlier reported quantitative structure-activity relationship studies, a series of 9beta-16-(arylalkyl)-10-deoxoartemisinins were proposed for synthesis. Several of the new compounds 7 and 10-14 were synthesized, employing the key synthetic intermediate 23. In a second approach, the natural product (+)-artemisinic acid was utilized as an acceptor for conjugate addition, and the resultant homologated acids were subjected to singlet oxygenation and acid treatment to provide artemisinin analogues. Under a new approach, we developed A one step reaction for the interconversion of artemisinin 1 into artemisitene 22 that did not employ selenium-based reagents and found that 2-arylethyliodides would undergo facile radical-induced conjugate addition to the exomethylene lactone of 22 in good yield. The lactone carbonyls, were removed sequentially by diisobutylaluminum hydride reduction followed directly by a second reduction (BF3-etherate/Et3SiH) to afford the desired corresponding pyrans. Six additional halogen-substituted aromatic side chains were installed via 22 furnishing the bioassay candidates 15-20. The analogues were examined for in vitro antimalarial activity in the W-2 and D-6 clones of Plasmodium falciparum and were additionally tested. in vivo in Plasmodium berghei- and/or Plasmodium yoelii-infected mice. Several of the compounds emerged as highly potent orally active candidates without obvious toxicity, Of these, two were chosen for pharmacokinetic evaluation, 14 and 17.

  DOI：

  10.1021/jm020142z
• 作为产物：
  描述：

  青蒿素 在 copper(l) iodide 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 间氯过氧苯甲酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 32.0h， 生成 (+)-octahydro-3,6α-dimethyl-3,12-epoxy-9β-(3'-(trifluoromethyl)propyl)-12H-pyrano[4,3j]-1,2-benzodioxepin-10(3H)-one
  参考文献：
  名称：

  Structure−Activity Relationships of the Antimalarial Agent Artemisinin. 7. Direct Modification of (+)-Artemisinin and In Vivo Antimalarial Screening of New, Potential Preclinical Antimalarial Candidates

  摘要：

  On the basis of earlier reported quantitative structure-activity relationship studies, a series of 9beta-16-(arylalkyl)-10-deoxoartemisinins were proposed for synthesis. Several of the new compounds 7 and 10-14 were synthesized, employing the key synthetic intermediate 23. In a second approach, the natural product (+)-artemisinic acid was utilized as an acceptor for conjugate addition, and the resultant homologated acids were subjected to singlet oxygenation and acid treatment to provide artemisinin analogues. Under a new approach, we developed A one step reaction for the interconversion of artemisinin 1 into artemisitene 22 that did not employ selenium-based reagents and found that 2-arylethyliodides would undergo facile radical-induced conjugate addition to the exomethylene lactone of 22 in good yield. The lactone carbonyls, were removed sequentially by diisobutylaluminum hydride reduction followed directly by a second reduction (BF3-etherate/Et3SiH) to afford the desired corresponding pyrans. Six additional halogen-substituted aromatic side chains were installed via 22 furnishing the bioassay candidates 15-20. The analogues were examined for in vitro antimalarial activity in the W-2 and D-6 clones of Plasmodium falciparum and were additionally tested. in vivo in Plasmodium berghei- and/or Plasmodium yoelii-infected mice. Several of the compounds emerged as highly potent orally active candidates without obvious toxicity, Of these, two were chosen for pharmacokinetic evaluation, 14 and 17.

  DOI：

  10.1021/jm020142z