4'-demethyl-9-deoxysikkimotoxin | 581801-49-2

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 木脂素内酯
• 英文名称: 4'-demethyl-9-deoxysikkimotoxin
• CAS: 581801-49-2
• 化学式: C₂₂H₂₄O₇
• 分子量: 400.428
• InChiKey: GMHCFROSGPWZJW-SVIJTADQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  29.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  83.45
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  4'-demethyl-9-deoxysikkimotoxin 在 sodium periodate 、 disodium hydrogenphosphate 、 lithium aluminium tetrahydride 、 sodium dithionite 作用下， 以 四氢呋喃 、 氯仿 、 水 、 丙酮 为溶剂， 反应 9.5h， 生成 ((6aR,7R,12bS)-2,3,4,10,11-Pentamethoxy-6a,7,8,12b-tetrahydro-6H-5-oxa-benzo[c]phenanthren-7-yl)-methanol
  参考文献：
  名称：

  Modes of Methyleneoxy Bridging and Their Effect on Tetrahydronaphthalene Lignan Cytotoxicity

  摘要：

  Dioxatricyclodecane, oxabicyclooctane, and benzodihydropyran derivatives of alpha-conidendrin (ACON), podophyllotoxin (PT), and sikkimotoxin (SK) were prepared to learn which methyleneoxy bridging modes and arene and aryl substituents coincided with high cytotoxicity. PT-derived dioxatricyclodecane 14 showed in vitro activity at 10(-8) M. SK analogue 12 was less active, and ACON analogue 11 was inactive at 10(-4) M. In vivo intraperitoneal and subcutaneous activities of 14 were observed. In vitro cytotoxicities were higher for oxabicyclooctanes when hydroxymethyl group and methyleneoxy bridge were cis, as in deoxypicropodophyllin analog 20, rather than trans, as in PT analogue 5. Acetylation of the hydroxymethyl group of 20 lowered activities, whereas acetylation of 5 increased or lowered activities. Reduction of the hydroxymethyl group of 5 to a methyl group increased cytotoxicities. Molecular dynamics indicated the THN scaffold of benzodihydropyrans was conformationally mobile, but scaffolds of oxabicyclooctanes and dioxatricyclodecanes were immobile. Each of three PT-benzodihydropyrans was less active than its oxabicyclooctane counterpart.

  DOI：

  10.1021/jm020158p
• 作为产物：
  描述：

  9-deoxysikkimotoxin 在 氢溴酸 、 溶剂黄146 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 13.7h， 以64%的产率得到4'-demethyl-9-deoxysikkimotoxin
  参考文献：
  名称：

  Modes of Methyleneoxy Bridging and Their Effect on Tetrahydronaphthalene Lignan Cytotoxicity

  摘要：

  Dioxatricyclodecane, oxabicyclooctane, and benzodihydropyran derivatives of alpha-conidendrin (ACON), podophyllotoxin (PT), and sikkimotoxin (SK) were prepared to learn which methyleneoxy bridging modes and arene and aryl substituents coincided with high cytotoxicity. PT-derived dioxatricyclodecane 14 showed in vitro activity at 10(-8) M. SK analogue 12 was less active, and ACON analogue 11 was inactive at 10(-4) M. In vivo intraperitoneal and subcutaneous activities of 14 were observed. In vitro cytotoxicities were higher for oxabicyclooctanes when hydroxymethyl group and methyleneoxy bridge were cis, as in deoxypicropodophyllin analog 20, rather than trans, as in PT analogue 5. Acetylation of the hydroxymethyl group of 20 lowered activities, whereas acetylation of 5 increased or lowered activities. Reduction of the hydroxymethyl group of 5 to a methyl group increased cytotoxicities. Molecular dynamics indicated the THN scaffold of benzodihydropyrans was conformationally mobile, but scaffolds of oxabicyclooctanes and dioxatricyclodecanes were immobile. Each of three PT-benzodihydropyrans was less active than its oxabicyclooctane counterpart.

  DOI：

  10.1021/jm020158p