(1R,2R)-1,2-dihydroxy-1-(3--4-methoxyphenyl)-2-(3',4',5'-trimethoxyphenyl)ethane | 226990-05-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 缩酚酸和缩酚酸环醚类
• 英文名称: (1R,2R)-1,2-dihydroxy-1-(3--4-methoxyphenyl)-2-(3',4',5'-trimethoxyphenyl)ethane
• 英文别名: [5-[(1R,2R)-1,2-dihydroxy-2-(3,4,5-trimethoxyphenyl)ethyl]-2-methoxyphenyl] 4-bromobenzoate
• CAS: 226990-05-2
• 化学式: C₂₅H₂₅BrO₈
• 分子量: 533.373
• InChiKey: FAOLRVAWEPYIJP-DHIUTWEWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  乙酸酐 、 (1R,2R)-1,2-dihydroxy-1-(3--4-methoxyphenyl)-2-(3',4',5'-trimethoxyphenyl)ethane 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以91%的产率得到(1R,2R)-1,2-diacetoxy-1-(3--4-methoxyphenyl)-2-(3',4',5'-trimethoxyphenyl)ethane
  参考文献：
  名称：

  Antineoplastic Agents. 410. Asymmetric Hydroxylation of trans-Combretastatin A-4

  摘要：

  The South African willow tree Combretum caffrum has yielded a number of potent cancer cell growth inhibitors. The present SAR studies of the antineoplastic agent combretastatin A-4 (1c) were focused mainly on the olefinic bridge to determine the effects on cancer cell growth and, potentially, to better define the combretastatin A-4 binding site on tubulin. The geometric trans-isomer 3a of combretastatin A-4 was converted to the (1S,2S)- and (1R,2R)-vicinal diols 4c and 4d, respectively, under Sharpless' asymmetric dihydroxylation conditions. Cancer cell line testing showed the (1S,2S)-diol 4c to be more potent than its enantiomer 4d. Diol 4c weakly inhibited tubulin polymerization (IC50 = 22 mu M, versus 1.2 mu M for combretastatin A-4), while 4d was inactive (IC50 > 40 mu M). Esterification of either stereoisomer at the diol and/or phenolic positions resulted in elimination of inhibitory activity.

  DOI：

  10.1021/jm9807149
• 作为产物：
  描述：

  (E)-1-(3',4',5'-Trimethoxyphenyl)-2-(4''-methoxy-3''-tert-butyldimethylsiloxyphenyl)ethene 在 甲基磺酰胺 、 四丁基氟化铵 、 三乙胺 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 、 正丁醇 为溶剂， 反应 74.5h， 生成 (1R,2R)-1,2-dihydroxy-1-(3--4-methoxyphenyl)-2-(3',4',5'-trimethoxyphenyl)ethane
  参考文献：
  名称：

  Antineoplastic Agents. 410. Asymmetric Hydroxylation of trans-Combretastatin A-4

  摘要：

  The South African willow tree Combretum caffrum has yielded a number of potent cancer cell growth inhibitors. The present SAR studies of the antineoplastic agent combretastatin A-4 (1c) were focused mainly on the olefinic bridge to determine the effects on cancer cell growth and, potentially, to better define the combretastatin A-4 binding site on tubulin. The geometric trans-isomer 3a of combretastatin A-4 was converted to the (1S,2S)- and (1R,2R)-vicinal diols 4c and 4d, respectively, under Sharpless' asymmetric dihydroxylation conditions. Cancer cell line testing showed the (1S,2S)-diol 4c to be more potent than its enantiomer 4d. Diol 4c weakly inhibited tubulin polymerization (IC50 = 22 mu M, versus 1.2 mu M for combretastatin A-4), while 4d was inactive (IC50 > 40 mu M). Esterification of either stereoisomer at the diol and/or phenolic positions resulted in elimination of inhibitory activity.

  DOI：

  10.1021/jm9807149

文献信息

• Antineoplastic Agents. 410. Asymmetric Hydroxylation of <i>trans</i>-Combretastatin A-4
  作者：George R. Pettit、Brian E. Toki、Delbert L. Herald、Michael R. Boyd、Ernest Hamel、Robin K. Pettit、J. Charles Chapuis

  DOI：10.1021/jm9807149

  日期：1999.4.22

  The South African willow tree Combretum caffrum has yielded a number of potent cancer cell growth inhibitors. The present SAR studies of the antineoplastic agent combretastatin A-4 (1c) were focused mainly on the olefinic bridge to determine the effects on cancer cell growth and, potentially, to better define the combretastatin A-4 binding site on tubulin. The geometric trans-isomer 3a of combretastatin A-4 was converted to the (1S,2S)- and (1R,2R)-vicinal diols 4c and 4d, respectively, under Sharpless' asymmetric dihydroxylation conditions. Cancer cell line testing showed the (1S,2S)-diol 4c to be more potent than its enantiomer 4d. Diol 4c weakly inhibited tubulin polymerization (IC50 = 22 mu M, versus 1.2 mu M for combretastatin A-4), while 4d was inactive (IC50 > 40 mu M). Esterification of either stereoisomer at the diol and/or phenolic positions resulted in elimination of inhibitory activity.