(2S,3S,5S,6S)-methyl 6-(3-(benzyloxy)-5-bromophenyl)-3-methoxy-5-methyltetrahydro-2H-pyran-2-carboxylate | 1225609-09-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2S,3S,5S,6S)-methyl 6-(3-(benzyloxy)-5-bromophenyl)-3-methoxy-5-methyltetrahydro-2H-pyran-2-carboxylate
• 英文别名: methyl (2S,3S,5S,6S)-6-(3-bromo-5-phenylmethoxyphenyl)-3-methoxy-5-methyloxane-2-carboxylate
• CAS: 1225609-09-5
• 化学式: C₂₂H₂₅BrO₅
• 分子量: 449.341
• InChiKey: LFCXJBVLLGYTQC-CXTHYWKRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S,3S,5S,6S)-methyl 6-(3-(benzyloxy)-5-bromophenyl)-3-methoxy-5-methyltetrahydro-2H-pyran-2-carboxylate 在 锂硼氢 、 水 作用下， 以 乙醚 为溶剂， 反应 1.5h， 以89%的产率得到((2R,3S,5S,6S)-6-(3-(benzyloxy)-5-bromophenyl)-3-methoxy-5-methyltetrahydro-2H-pyran-2-yl)methanol
  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：

  (2S,3S,5S,6S)-methyl 6-(3-(benzyloxy)-5-bromophenyl)-3-hydroxy-5-methyltetrahydro-2H-pyran-2-carboxylate 、 trimethoxonium tetrafluoroborate 在 1,8-双二甲氨基萘 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以90.1%的产率得到(2S,3S,5S,6S)-methyl 6-(3-(benzyloxy)-5-bromophenyl)-3-methoxy-5-methyltetrahydro-2H-pyran-2-carboxylate
  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).