(2E,6S,7S,8E,10S,11R,12S,14R)-15-(3-(benzyloxy)-5-bromo-2-methoxyphenyl)-7-(tert-butyldimethylsilyloxy)-6,12-dimethoxy-11-(methoxymethoxy)-2,8,10,14-tetramethylpentadeca-2,8-dienamide | 869732-09-2

• 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: (2E,6S,7S,8E,10S,11R,12S,14R)-15-(3-(benzyloxy)-5-bromo-2-methoxyphenyl)-7-(tert-butyldimethylsilyloxy)-6,12-dimethoxy-11-(methoxymethoxy)-2,8,10,14-tetramethylpentadeca-2,8-dienamide
• 英文别名: (2E,6S,7S,8E,10S,11R,12S,14R)-15-(5-bromo-2-methoxy-3-phenylmethoxyphenyl)-7-[tert-butyl(dimethyl)silyl]oxy-6,12-dimethoxy-11-(methoxymethoxy)-2,8,10,14-tetramethylpentadeca-2,8-dienamide
• CAS: 869732-09-2
• 化学式: C₄₃H₆₈BrNO₈Si
• 分子量: 835.004
• InChiKey: VZCRCAVUZJCZBL-QRCRGKBLSA-N

物化性质

• 沸点：
  791.5±60.0 °C(Predicted)
• 密度：
  1.112±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  9.81
• 重原子数：
  54
• 可旋转键数：
  25
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  108
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (2E,6S,7S,8E,10S,11R,12S,14R)-15-(3-(benzyloxy)-5-bromo-2-methoxyphenyl)-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83%的产率得到(4E,8S,9S,10E,12S,13R,14S,16R)-20-(benzyloxy)-9-(tert-butyldimethylsilyloxy)-13-(methoxymethoxy)-4,10,12,16-tetramethyl-8,14,19-trimethoxy-2-aza-bicyclo[16.3.1]docosa-1(21),4,10,18(22),19-pentaen-3-one
  参考文献：
  名称：

  Total Synthesis of Reblastatin

  摘要：

  Enantioselective total synthesis of reblastatin is described. The synthesis highlights hydrozirconation, transmetalation, aldehyde addition sequence to install E-trisubstituted olefin and C7 stereocenter, and the first use of an intramolecular Buchwald-like amidation reaction to close the 19-membered macrolactam.

  DOI：

  10.1021/ja055384d
• 作为产物：
  描述：

  L-谷氨酸 在 咪唑 、 2,6-二甲基吡啶 、 盐酸 、 lithium hydroxide 、 Schwartz's reagent 、 草酰氯 、 dimethyl sulfide borane 、 4 A molecular sieve 、 Proton-Sponge 、 氯甲酸乙酯 、 二异丁基氢化铝 、 二甲基亚砜 、 三乙胺 、 sodium nitrite 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 、 苯 为溶剂， 反应 73.5h， 生成 (2E,6S,7S,8E,10S,11R,12S,14R)-15-(3-(benzyloxy)-5-bromo-2-methoxyphenyl)-7-(tert-butyldimethylsilyloxy)-6,12-dimethoxy-11-(methoxymethoxy)-2,8,10,14-tetramethylpentadeca-2,8-dienamide
  参考文献：
  名称：

  Total Synthesis of Reblastatin

  摘要：

  Enantioselective total synthesis of reblastatin is described. The synthesis highlights hydrozirconation, transmetalation, aldehyde addition sequence to install E-trisubstituted olefin and C7 stereocenter, and the first use of an intramolecular Buchwald-like amidation reaction to close the 19-membered macrolactam.

  DOI：

  10.1021/ja055384d

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).