(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-carbamic acid 13,20-dihydroxy-8,14,19-trimethoxy-4,10,12,16-tetramethyl-3-oxo-2-aza-bicyclo[16.3.1]docosa-1(21),4,6,10,18(22),19-hexaen-9-yl ester | 1225609-66-4

• 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,6Z,8S,9S,10E,12S,13R,14S,16R)-carbamic acid 13,20-dihydroxy-8,14,19-trimethoxy-4,10,12,16-tetramethyl-3-oxo-2-aza-bicyclo[16.3.1]docosa-1(21),4,6,10,18(22),19-hexaen-9-yl ester
• 英文别名: [(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-13,20-dihydroxy-8,14,19-trimethoxy-4,10,12,16-tetramethyl-3-oxo-2-azabicyclo[16.3.1]docosa-1(22),4,6,10,18,20-hexaen-9-yl] carbamate
• CAS: 1225609-66-4
• 化学式: C₂₉H₄₂N₂O₈
• 分子量: 546.661
• InChiKey: GULKMGRAQDRMKW-CMPYOTJFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  39
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  150
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (4E,6Z,8S,9S,10E,12S,13R,14S,16R)-15-(benzyloxy)-14,8,14-trimethoxy-13-(methoxymethoxy)-4,10,12,16-tetramethyl-3-oxo-2-aza-1(1,3)-benzenacycloheptadecaphane-4,6,10-trien-9-yl carbamate 在 aluminum (III) chloride 、 苯甲醚 、 盐酸 作用下， 以 二氯甲烷 、 水 为溶剂， 以75%的产率得到(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-carbamic acid 13,20-dihydroxy-8,14,19-trimethoxy-4,10,12,16-tetramethyl-3-oxo-2-aza-bicyclo[16.3.1]docosa-1(21),4,6,10,18(22),19-hexaen-9-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

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).