(1R,4S,5R,8S,9R,12S,13R)-9-[3-(3,4-dichlorophenyl)propyl]-1,5-dimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-one | 467223-76-3

• 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: (1R,4S,5R,8S,9R,12S,13R)-9-[3-(3,4-dichlorophenyl)propyl]-1,5-dimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-one
• CAS: 467223-76-3
• 化学式: C₂₃H₂₈Cl₂O₅
• 分子量: 455.378
• InChiKey: WZNYKRWGCGKNCF-RIMQOSICSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (1R,4S,5R,8S,9R,12S,13R)-9-[3-(3,4-dichlorophenyl)propyl]-1,5-dimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-one 在 三乙基硅烷 、 二异丁基氢化铝 作用下， 以 正己烷 、 二氯甲烷 为溶剂， 反应 4.42h， 生成 (+)-octahydro-3,6α-dimethyl-3,12-epoxy-9β-(3'-(3,4-dichlorophenyl)propyl)-12H-pyrano[4,3j]-1,2-benzodioxepin
  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：

  (1''S,1'''R,3''S,6''R)-(2''E)-2-[2'-[3''-(1'''-carboxy-4'''-3,4-dichlorophenylbutyl)-6''-methyl-2''-[(trimethylsilyl)methylene]cyclohexyl]ethyl]-2,5,5-trimethyl-1,3-dioxane 在 臭氧 、 硫酸 、 silica gel 作用下， 以 二氯甲烷 为溶剂， -78.0~20.0 ℃ 、48.26 kPa 条件下， 以31%的产率得到(1R,4S,5R,8S,9R,12S,13R)-9-[3-(3,4-dichlorophenyl)propyl]-1,5-dimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-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

文献信息

• Structure−Activity Relationships of the Antimalarial Agent Artemisinin. 7. Direct Modification of (+)-Artemisinin and In Vivo Antimalarial Screening of New, Potential Preclinical Antimalarial Candidates
  作者：Mitchell A. Avery、Maria Alvim-Gaston、Jeffrey A. Vroman、Baogen Wu、Arba Ager、Wallace Peters、Brian L. Robinson、William Charman

  DOI：10.1021/jm020142z

  日期：2002.9.1

  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.