1-(benzyloxy)-3-bromo-5-((2R,4S,5R,6S)-4-methoxy-5-(methoxymethoxy)-2,6-dimethylnon-7-ynyl)benzene | 1225609-24-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(benzyloxy)-3-bromo-5-((2R,4S,5R,6S)-4-methoxy-5-(methoxymethoxy)-2,6-dimethylnon-7-ynyl)benzene
• 英文别名: 1-bromo-3-[(2R,4S,5R,6S)-4-methoxy-5-(methoxymethoxy)-2,6-dimethylnon-7-ynyl]-5-phenylmethoxybenzene
• CAS: 1225609-24-4
• 化学式: C₂₇H₃₅BrO₄
• 分子量: 503.476
• InChiKey: ZRWROPCWUIDFFE-KXLSXUBNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  32
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  36.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (6S,2E)-ethyl 6-methoxy-2-methyl-7-oxohept-2-enoate 、 1-(benzyloxy)-3-bromo-5-((2R,4S,5R,6S)-4-methoxy-5-(methoxymethoxy)-2,6-dimethylnon-7-ynyl)benzene 在 Schwartz's reagent 、 Dimethylzinc 作用下， 以 甲苯 为溶剂， 反应 6.0h， 以55%的产率得到ethyl (2E,6S,7S,8E,10S,11R,12S,14R)-15-(3-bromo-5-phenylmethoxyphenyl)-7-hydroxy-6,12-dimethoxy-11-(methoxymethoxy)-2,8,10,14-tetramethylpentadeca-2,8-dienoate
  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：

  1-(benzyloxy)-3-bromo-5-((2R,4S,5R,6S)-4-methoxy-5-(methoxymethoxy)-2,6-dimethyloct-7-ynyl)benzene 、 碘甲烷 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 以92%的产率得到1-(benzyloxy)-3-bromo-5-((2R,4S,5R,6S)-4-methoxy-5-(methoxymethoxy)-2,6-dimethylnon-7-ynyl)benzene
  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).