(1''S,1'''R,3''S,6''R)-(2''E)-2-[2'-[3''-(1'''-carboxy-4'''-p-fluorophenylbutyl)-6''-methyl-2''-[(trimethylsilyl)methylene]cyclohexyl]ethyl]-2,5,5-trimethyl-1,3-dioxane | 467223-71-8

• 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: (1''S,1'''R,3''S,6''R)-(2''E)-2-[2'-[3''-(1'''-carboxy-4'''-p-fluorophenylbutyl)-6''-methyl-2''-[(trimethylsilyl)methylene]cyclohexyl]ethyl]-2,5,5-trimethyl-1,3-dioxane
• CAS: 467223-71-8
• 化学式: C₃₁H₄₉FO₄Si
• 分子量: 532.812
• InChiKey: WIVUGIPGWGASAY-HNZPRQNBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.88
• 重原子数：
  37.0
• 可旋转键数：
  10.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  55.76
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (1''S,1'''R,3''S,6''R)-(2''E)-2-[2'-[3''-(1'''-carboxy-4'''-p-fluorophenylbutyl)-6''-methyl-2''-[(trimethylsilyl)methylene]cyclohexyl]ethyl]-2,5,5-trimethyl-1,3-dioxane 在 二异丁基氢化铝 、 臭氧 作用下， 以 正己烷 、 二氯甲烷 为溶剂， -78.0~20.0 ℃ 、48.26 kPa 条件下， 反应 1.25h， 生成
  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：

  2,5,5-trimethyl-2-<2'-<4''-(carboxymethyl)-1''(R)-methyl-3''-<(trimethylsilyl)methylene>cyclohex-2''-yl>ethyl>-1,3-dioxane 、 alkaline earth salt of/the/ methylsulfuric acid 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 5.17h， 以75%的产率得到(1''S,1'''R,3''S,6''R)-(2''E)-2-[2'-[3''-(1'''-carboxy-4'''-p-fluorophenylbutyl)-6''-methyl-2''-[(trimethylsilyl)methylene]cyclohexyl]ethyl]-2,5,5-trimethyl-1,3-dioxane
  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