(4E,8S,9S,10E,12S,13R,14S,16R)-15-(benzyloxy)-14,8,14-trimethoxy-4,10,12,16-tetramethyl-3-oxo-2-aza-1(1,3)-benzenacycloheptadecaphane-4,10-diene-9,13-diyl dicarbamate | 1225609-72-2

• 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)-15-(benzyloxy)-14,8,14-trimethoxy-4,10,12,16-tetramethyl-3-oxo-2-aza-1(1,3)-benzenacycloheptadecaphane-4,10-diene-9,13-diyl dicarbamate
• CAS: 1225609-72-2
• 化学式: C₃₇H₅₁N₃O₉
• 分子量: 681.827
• InChiKey: JBEYPZYJVUIKFV-RJSXDIEASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.06
• 重原子数：
  49.0
• 可旋转键数：
  8.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  170.66
• 氢给体数：
  3.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  (4E,8S,9S,10E,12S,13R,14S,16R)-15-(benzyloxy)-14,8,14-trimethoxy-4,10,12,16-tetramethyl-3-oxo-2-aza-1(1,3)-benzenacycloheptadecaphane-4,10-diene-9,13-diyl dicarbamate 在 aluminum (III) chloride 、 苯甲醚 、 盐酸 作用下， 以 二氯甲烷 、 水 为溶剂， 以66%的产率得到(4E,8S,9S,10E,12S,13R,14S,16R)-bis-carbamic acid 20-(hydroxy)-8,14,19-trimethoxy-4,10,12,16-tetramethyl-3-oxo-2-aza-bicyclo[16.3.1]docosa-1(21),4,10,18(22),19-pentaen-9,13-yl ester
  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：

  (4E,8S,9S,10E,12S,13R,14S,16R)-15-(benzyloxy)-9,13-dihydroxy-14,8,14-trimethoxy-4,10,12,16-tetramethyl-2-aza-1(1,3)-benzenacycloheptadecaphane-4,10-dien-3-one 、 三氯乙酰异氰酸酯 在 potassium carbonate 作用下， 以 二氯甲烷 、 甲醇 、 dichloromethaneq 为溶剂， 反应 1.25h， 以94%的产率得到(4E,8S,9S,10E,12S,13R,14S,16R)-15-(benzyloxy)-14,8,14-trimethoxy-4,10,12,16-tetramethyl-3-oxo-2-aza-1(1,3)-benzenacycloheptadecaphane-4,10-diene-9,13-diyl dicarbamate
  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