(2S,5R,6R,9R)-2-(3,4-dimethoxyphenyl)-12,13-dimethoxy-3,8-dioxatetracyclo[8.4.0.02,6.05,9]tetradeca-1(14),10,12-triene

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 芳基四氢萘木脂素
• 英文名称: (2S,5R,6R,9R)-2-(3,4-dimethoxyphenyl)-12,13-dimethoxy-3,8-dioxatetracyclo[8.4.0.02,6.05,9]tetradeca-1(14),10,12-triene
• 化学式: C₂₂H₂₄O₆
• 分子量: 384.429
• InChiKey: UHFKQQZCYSTODS-GYISASMLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  55.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  r-1-(3,4-dimethoxyphenyl)-t-2,c-3-bis(hydroxymethyl)-6,7-dimethoxy-1,2,3,4-tetrahydronaphthalene 在 dipotassium peroxodisulfate 、 copper(II) sulfate 作用下， 以 水 、 乙腈 为溶剂， 反应 0.5h， 以38%的产率得到(2S,5R,6R,9R)-2-(3,4-dimethoxyphenyl)-12,13-dimethoxy-3,8-dioxatetracyclo[8.4.0.02,6.05,9]tetradeca-1(14),10,12-triene
  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

文献信息

• Modes of Methyleneoxy Bridging and Their Effect on Tetrahydronaphthalene Lignan Cytotoxicity
  作者：Robert T. LaLonde、Frank Ramdayal、Anatole Sarko、Koichi Yanai、Mianji Zhang

  DOI：10.1021/jm020158p

  日期：2003.3.1

  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.