(1S,2S)-1-[3-(tert-Butyl-dimethyl-silanyloxy)-4-methoxy-phenyl]-2-(3,4,5-trimethoxy-phenyl)-ethane-1,2-diol | 226989-87-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: (1S,2S)-1-[3-(tert-Butyl-dimethyl-silanyloxy)-4-methoxy-phenyl]-2-(3,4,5-trimethoxy-phenyl)-ethane-1,2-diol
• 英文别名: (1S,2S)-1-[3-[tert-butyl(dimethyl)silyl]oxy-4-methoxyphenyl]-2-(3,4,5-trimethoxyphenyl)ethane-1,2-diol
• CAS: 226989-87-3
• 化学式: C₂₄H₃₆O₇Si
• 分子量: 464.631
• InChiKey: LWMRWPBWSYSVCW-VXKWHMMOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.87
• 重原子数：
  32
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  86.6
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (1S,2S)-1-[3-(tert-Butyl-dimethyl-silanyloxy)-4-methoxy-phenyl]-2-(3,4,5-trimethoxy-phenyl)-ethane-1,2-diol 在 吡啶 、 四丁基氟化铵 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 20.5h， 生成 (1S,2S)-1,2-di(p-bromobenzoyloxy)-1-(3-hydroxy-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 作用下， 以 水 、 正丁醇 为溶剂， 反应 72.0h， 以88%的产率得到(1S,2S)-1-[3-(tert-Butyl-dimethyl-silanyloxy)-4-methoxy-phenyl]-2-(3,4,5-trimethoxy-phenyl)-ethane-1,2-diol
  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.