(4E,8S,9S,10E,12S,13R,14S,16R)-20-(benzyloxy)-9-(tert-butyldimethylsilyloxy)-8,14-dimethoxy-13-(methoxymethoxy)-4,10,12,16-tetramethyl-2-aza-bicyclo[16.3.1]docosa-1(21),4,10,18(22),19-pentaen-3-on | 1225609-43-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 英文名称: (4E,8S,9S,10E,12S,13R,14S,16R)-20-(benzyloxy)-9-(tert-butyldimethylsilyloxy)-8,14-dimethoxy-13-(methoxymethoxy)-4,10,12,16-tetramethyl-2-aza-bicyclo[16.3.1]docosa-1(21),4,10,18(22),19-pentaen-3-on
• 英文别名: (4E,8S,9S,10E,12S,13R,14S,16R)-9-[tert-butyl(dimethyl)silyl]oxy-8,14-dimethoxy-13-(methoxymethoxy)-4,10,12,16-tetramethyl-20-phenylmethoxy-2-azabicyclo[16.3.1]docosa-1(21),4,10,18(22),19-pentaen-3-one
• CAS: 1225609-43-7
• 化学式: C₄₂H₆₅NO₇Si
• 分子量: 724.066
• InChiKey: FSBQIDNRVXYPLZ-KAUOCMFESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.5
• 重原子数：
  51
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  84.5
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (4E,8S,9S,10E,12S,13R,14S,16R)-20-(benzyloxy)-9-(tert-butyldimethylsilyloxy)-8,14-dimethoxy-13-(methoxymethoxy)-4,10,12,16-tetramethyl-2-aza-bicyclo[16.3.1]docosa-1(21),4,10,18(22),19-pentaen-3-on 在 吡啶 、 氟化氢吡啶 、 碳酸氢钠 作用下， 以 四氢呋喃 为溶剂， 生成 (4E,8S,9S,10E,12S,13R,14S,16R)-9-hydroxy-8,14-dimethoxy-13-(methoxymethoxy)-4,10,12,16-tetramethyl-20-phenylmethoxy-2-azabicyclo[16.3.1]docosa-1(21),4,10,18(22),19-pentaen-3-one
  参考文献：
  名称：

  Synthesis of Reblastatin, Autolytimycin, and Non-Benzoquinone Analogues: Potent Inhibitors of Heat Shock Protein 90

  摘要：

  A full account of an asymmetric synthesis of reblastatin (1) and the first total synthesis of autolytimycin (2) and related structural compounds is described. The syntheses expand the utility of a highly regio- and diastereoselective hydrometalation aldehyde addition sequence to assemble the fully functionalized ansa chain of the natural products. Also documented is an intramolecular copper-mediated amidation reaction to close the 19-membered macrolactams. The amidation reaction was also employed for the generation of structural derivatives (6-9) of phenolic ansamycins. Ansamycin natural products and selected structural analogues were evaluated in a competitive binding assay to breast cancer cell lysate and a cytotoxicity assay. Both reblastatin (1) and autolytimycin (2) were shown to bind the heat shock protein 90 with enhanced binding activity (similar to 25 nM) than 17-allylamino-17-demethoxygeldanamycin (17-AAG, 4), a geldanamycin (3) derivative currently under evaluation for treatment of cancer (similar to 100 nM).

  DOI：

  10.1021/jo1000109
• 作为产物：
  描述：

  (2E,6S,7S,8E,10S,12S,14R)-15-(3-(benzyloxy)-5-bromophenyl)-7-(tert-butyldimethylsilyloxy)-6,12-dimethoxy-11-(methoxymethoxy)-2,8,10,14-tetramethylpentadeca-2,8-dienamide 在 copper(l) iodide 、 potassium carbonate 、 N,N'-二甲基乙二胺 作用下， 以 甲苯 为溶剂， 反应 36.0h， 以82%的产率得到(4E,8S,9S,10E,12S,13R,14S,16R)-20-(benzyloxy)-9-(tert-butyldimethylsilyloxy)-8,14-dimethoxy-13-(methoxymethoxy)-4,10,12,16-tetramethyl-2-aza-bicyclo[16.3.1]docosa-1(21),4,10,18(22),19-pentaen-3-on
  参考文献：
  名称：

  Synthesis of Reblastatin, Autolytimycin, and Non-Benzoquinone Analogues: Potent Inhibitors of Heat Shock Protein 90

  摘要：

  A full account of an asymmetric synthesis of reblastatin (1) and the first total synthesis of autolytimycin (2) and related structural compounds is described. The syntheses expand the utility of a highly regio- and diastereoselective hydrometalation aldehyde addition sequence to assemble the fully functionalized ansa chain of the natural products. Also documented is an intramolecular copper-mediated amidation reaction to close the 19-membered macrolactams. The amidation reaction was also employed for the generation of structural derivatives (6-9) of phenolic ansamycins. Ansamycin natural products and selected structural analogues were evaluated in a competitive binding assay to breast cancer cell lysate and a cytotoxicity assay. Both reblastatin (1) and autolytimycin (2) were shown to bind the heat shock protein 90 with enhanced binding activity (similar to 25 nM) than 17-allylamino-17-demethoxygeldanamycin (17-AAG, 4), a geldanamycin (3) derivative currently under evaluation for treatment of cancer (similar to 100 nM).

  DOI：

  10.1021/jo1000109

文献信息

• Synthesis of Reblastatin, Autolytimycin, and Non-Benzoquinone Analogues: Potent Inhibitors of Heat Shock Protein 90
  作者：Iwona E. Wrona、Alexander Gozman、Tony Taldone、Gabriela Chiosis、James S. Panek

  DOI：10.1021/jo1000109

  日期：2010.5.7

  A full account of an asymmetric synthesis of reblastatin (1) and the first total synthesis of autolytimycin (2) and related structural compounds is described. The syntheses expand the utility of a highly regio- and diastereoselective hydrometalation aldehyde addition sequence to assemble the fully functionalized ansa chain of the natural products. Also documented is an intramolecular copper-mediated amidation reaction to close the 19-membered macrolactams. The amidation reaction was also employed for the generation of structural derivatives (6-9) of phenolic ansamycins. Ansamycin natural products and selected structural analogues were evaluated in a competitive binding assay to breast cancer cell lysate and a cytotoxicity assay. Both reblastatin (1) and autolytimycin (2) were shown to bind the heat shock protein 90 with enhanced binding activity (similar to 25 nM) than 17-allylamino-17-demethoxygeldanamycin (17-AAG, 4), a geldanamycin (3) derivative currently under evaluation for treatment of cancer (similar to 100 nM).