3-O-tert-butyldimethylsilyl-4,4',5-trimethoxy-3'-nitro-(E)-stilbene | 870274-52-5

• 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: 3-O-tert-butyldimethylsilyl-4,4',5-trimethoxy-3'-nitro-(E)-stilbene
• 英文别名: tert-butyl-[2,3-dimethoxy-5-[(E)-2-(4-methoxy-3-nitrophenyl)ethenyl]phenoxy]-dimethylsilane
• CAS: 870274-52-5
• 化学式: C₂₃H₃₁NO₆Si
• 分子量: 445.588
• InChiKey: YEURJYLYZNZYGA-MDZDMXLPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.18
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  82.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-O-tert-butyldimethylsilyl-4,4',5-trimethoxy-3'-nitro-(E)-stilbene 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以66%的产率得到2,3-dimethoxy-5-[(E)-2-(4-methoxy-3-nitrophenyl)ethenyl]phenol
  参考文献：
  名称：

  Antineoplastic Agents. 509. Synthesis of Fluorcombstatin Phosphate and Related 3-Halostilbenes^,1

  摘要：

  The present SAR study of combretastatin A-3 (3a) focused on replacement of the 3-hydroxyl group by a series of halogens. That approach with Z-stilbenes resulted in greatly enhanced (> 10-100-fold) cancer cell growth inhibition against a panel of human cancer cell lines and the murine P388 lymphocytic leukemia cell line. Synthesis of the 3-fluoro-Z-stilbene designated fluorcombstatin (11a) and its potassium 3'-O-phosphate derivative (16c) by the route 7 -> 8a -> 11a -> 14 -> 16c illustrates the general synthetic pathway. The 3'-O-phosphoric acid ester (15) of 3-bromo-Z-stilbene 13a was also converted to representative cation salts to evaluate the potential for improved aqueous solubility, and the potassium salt (16 mg/mL in water) proved most useful. The fluoro (11a), chloro (12a), and bromo (13a) halocombstatins were nearly equivalent to combretastatin A-4 (1a) as inhibitors of tubulin polymerization and of the binding of colchicine to tubulin. The tubulin binding in cell-free systems was also retained in human umbilical vein endothelial cells. All three halocombstatins retained the powerful human cancer cell line inhibitory activity of combretastatin A-4 (la) and proved superior to combretastatin A-3 (3a). In addition, the halocombstatins targeted Gram-positive bacteria and Cryptococcus neoformans.

  DOI：

  10.1021/np058038i
• 作为产物：
  描述：

  3-<(tert-butyldimethylsilyl)oxy>-4,5-dimethoxybenzaldehyde 、 (4-methoxy-3-nitrobenzyl)triphenylphosphonium bromide 在 sodium hydride 作用下， 以 甲苯 为溶剂， 反应 22.0h， 以55%的产率得到3-O-tert-butyldimethylsilyl-4,4',5-trimethoxy-3'-nitro-(Z)-stilbene
  参考文献：
  名称：

  Antineoplastic Agents. 509. Synthesis of Fluorcombstatin Phosphate and Related 3-Halostilbenes^,1

  摘要：

  The present SAR study of combretastatin A-3 (3a) focused on replacement of the 3-hydroxyl group by a series of halogens. That approach with Z-stilbenes resulted in greatly enhanced (> 10-100-fold) cancer cell growth inhibition against a panel of human cancer cell lines and the murine P388 lymphocytic leukemia cell line. Synthesis of the 3-fluoro-Z-stilbene designated fluorcombstatin (11a) and its potassium 3'-O-phosphate derivative (16c) by the route 7 -> 8a -> 11a -> 14 -> 16c illustrates the general synthetic pathway. The 3'-O-phosphoric acid ester (15) of 3-bromo-Z-stilbene 13a was also converted to representative cation salts to evaluate the potential for improved aqueous solubility, and the potassium salt (16 mg/mL in water) proved most useful. The fluoro (11a), chloro (12a), and bromo (13a) halocombstatins were nearly equivalent to combretastatin A-4 (1a) as inhibitors of tubulin polymerization and of the binding of colchicine to tubulin. The tubulin binding in cell-free systems was also retained in human umbilical vein endothelial cells. All three halocombstatins retained the powerful human cancer cell line inhibitory activity of combretastatin A-4 (la) and proved superior to combretastatin A-3 (3a). In addition, the halocombstatins targeted Gram-positive bacteria and Cryptococcus neoformans.

  DOI：

  10.1021/np058038i

文献信息

• Antineoplastic Agents. 509. Synthesis of Fluorcombstatin Phosphate and Related 3-Halostilbenes^,1
  作者：George R. Pettit、Mathew D. Minardi、Heidi J. Rosenberg、Ernest Hamel、Michael C. Bibby、Sandie W. Martin、M. Katherine Jung、Robin K. Pettit、Timothy J. Cuthbertson、Jean-Charles Chapuis

  DOI：10.1021/np058038i

  日期：2005.10.1

  The present SAR study of combretastatin A-3 (3a) focused on replacement of the 3-hydroxyl group by a series of halogens. That approach with Z-stilbenes resulted in greatly enhanced (> 10-100-fold) cancer cell growth inhibition against a panel of human cancer cell lines and the murine P388 lymphocytic leukemia cell line. Synthesis of the 3-fluoro-Z-stilbene designated fluorcombstatin (11a) and its potassium 3'-O-phosphate derivative (16c) by the route 7 -> 8a -> 11a -> 14 -> 16c illustrates the general synthetic pathway. The 3'-O-phosphoric acid ester (15) of 3-bromo-Z-stilbene 13a was also converted to representative cation salts to evaluate the potential for improved aqueous solubility, and the potassium salt (16 mg/mL in water) proved most useful. The fluoro (11a), chloro (12a), and bromo (13a) halocombstatins were nearly equivalent to combretastatin A-4 (1a) as inhibitors of tubulin polymerization and of the binding of colchicine to tubulin. The tubulin binding in cell-free systems was also retained in human umbilical vein endothelial cells. All three halocombstatins retained the powerful human cancer cell line inhibitory activity of combretastatin A-4 (la) and proved superior to combretastatin A-3 (3a). In addition, the halocombstatins targeted Gram-positive bacteria and Cryptococcus neoformans.