brefeldin A 4-O-glutaryl-7-O-tert-butyldimethylsilyl ether | 903503-46-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: brefeldin A 4-O-glutaryl-7-O-tert-butyldimethylsilyl ether
• 英文别名: 5-[[(1R,2R,3E,7S,11E,13S,15S)-15-[tert-butyl(dimethyl)silyl]oxy-7-methyl-5-oxo-6-oxabicyclo[11.3.0]hexadeca-3,11-dien-2-yl]oxy]-5-oxopentanoic acid
• CAS: 903503-46-8
• 化学式: C₂₇H₄₄O₇Si
• 分子量: 508.728
• InChiKey: DRETWYZJAJBQGG-IEIAZVCFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  99.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  brefeldin A 4-O-glutaryl-7-O-tert-butyldimethylsilyl ether 在 tert-butyl-ammonium fluoride 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 为溶剂， 反应 96.0h， 生成 brefeldin A 4-O-methyl glutarate
  参考文献：
  名称：

  Synthesis and Anticancer Activity of Brefeldin A Ester Derivatives

  摘要：

  Ester derivatives of brefeldin A ( BFA) were synthesized to determine which of its two hydroxyl groups could be modified while still maintaining biological activity. The compounds were tested for antiproliferative activity in the National Cancer Institute's 60 cancer cell line screen. Monoderivatization at the C4 and C7 alcohols was tolerated, yielding biologically active compounds, whereas the analogues derivatized at both positions were the least active in the series. Molecular modeling of the analogues revealed that both the C4 and C7 derivatives were well tolerated at the interface between ARF1 and its guanine nucleotide exchange factor ARNO. The Golgi-disruptive properties of the analogues were determined using fluorescence imaging assays. The BFA ester conjugates synthesized in this study were cytotoxic to cancer cells, and we have shown that the disruption of the Golgi complex is not necessary for cytotoxicity. The brefeldin A ester derivatives are potential anticancer agents.

  DOI：

  10.1021/jm0602817
• 作为产物：
  描述：

  布雷非德菌素 A 在 2,6-二甲基吡啶 、 4-二甲氨基吡啶 、 tert-butyl-ammonium fluoride 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 45.0h， 生成 brefeldin A 4-O-glutaryl-7-O-tert-butyldimethylsilyl ether
  参考文献：
  名称：

  Synthesis and Anticancer Activity of Brefeldin A Ester Derivatives

  摘要：

  Ester derivatives of brefeldin A ( BFA) were synthesized to determine which of its two hydroxyl groups could be modified while still maintaining biological activity. The compounds were tested for antiproliferative activity in the National Cancer Institute's 60 cancer cell line screen. Monoderivatization at the C4 and C7 alcohols was tolerated, yielding biologically active compounds, whereas the analogues derivatized at both positions were the least active in the series. Molecular modeling of the analogues revealed that both the C4 and C7 derivatives were well tolerated at the interface between ARF1 and its guanine nucleotide exchange factor ARNO. The Golgi-disruptive properties of the analogues were determined using fluorescence imaging assays. The BFA ester conjugates synthesized in this study were cytotoxic to cancer cells, and we have shown that the disruption of the Golgi complex is not necessary for cytotoxicity. The brefeldin A ester derivatives are potential anticancer agents.

  DOI：

  10.1021/jm0602817

文献信息

• Synthesis and Anticancer Activity of Brefeldin A Ester Derivatives
  作者：Nwanne O. Anadu、V. Jo Davisson、Mark Cushman

  DOI：10.1021/jm0602817

  日期：2006.6.1

  Ester derivatives of brefeldin A ( BFA) were synthesized to determine which of its two hydroxyl groups could be modified while still maintaining biological activity. The compounds were tested for antiproliferative activity in the National Cancer Institute's 60 cancer cell line screen. Monoderivatization at the C4 and C7 alcohols was tolerated, yielding biologically active compounds, whereas the analogues derivatized at both positions were the least active in the series. Molecular modeling of the analogues revealed that both the C4 and C7 derivatives were well tolerated at the interface between ARF1 and its guanine nucleotide exchange factor ARNO. The Golgi-disruptive properties of the analogues were determined using fluorescence imaging assays. The BFA ester conjugates synthesized in this study were cytotoxic to cancer cells, and we have shown that the disruption of the Golgi complex is not necessary for cytotoxicity. The brefeldin A ester derivatives are potential anticancer agents.