(2E,6S,7S,8E,10S,11R,12S,14R)-15-(3-(benzyloxy)-5-bromo-2-methoxyphenyl)-7-((tert-butyldimethylsilyl)oxy)-6,12-dimethoxy-11-(methoxymethoxy)-2,8,10,14-tetramethylpentadeca-2,8-dienoic acid | 869732-33-2

• 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-butyldimethylsilyl)oxy)-6,12-dimethoxy-11-(methoxymethoxy)-2,8,10,14-tetramethylpentadeca-2,8-dienoic acid
• CAS: 869732-33-2
• 化学式: C₄₃H₆₇BrO₉Si
• 分子量: 835.989
• InChiKey: MJILGWUZRUQFQL-QRCRGKBLSA-N

物化性质

• 沸点：
  779.9±60.0 °C(Predicted)
• 密度：
  1.123±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  10.41
• 重原子数：
  54.0
• 可旋转键数：
  24.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  101.91
• 氢给体数：
  1.0
• 氢受体数：
  8.0

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-butyldimethylsilyl)oxy)-6,12-dimethoxy-11-(methoxymethoxy)-2,8,10,14-tetramethylpentadeca-2,8-dienoic acid 在 吡啶 、 二碳酸二叔丁酯 、 碳酸氢铵 作用下， 以 1,4-二氧六环 为溶剂， 反应 18.25h， 以80%的产率得到(2E,6S,7S,8E,10S,11R,12S,14R)-15-(3-(benzyloxy)-5-bromo-2-methoxyphenyl)-7-((tert-butyldimethylsilyl)oxy)-6,12-dimethoxy-11-(methoxymethoxy)-2,8,10,14-tetramethylpentadeca-2,8-dienamide
  参考文献：
  名称：

  Total synthesis of reblastatin: convenient preparation of coupling partners and scaled assembly

  摘要：

  Potentially scalable total synthesis of reblastatin was achieved based on Panek's previous study. Novel and convenient synthetic routes were developed for the known C8-C20 and C1-C7 coupling partners. The challenging C8-C20 fragment was prepared from TBS protected (S)-5-(hydroxymethyl)dihydrofuran-2(3H)-one (6) in nine steps (20% overall yield), and the C1-C7 fragment was synthesized from commercially available 3,4,6-tri-O-acetyl-D-glucal (9) in eight steps (35% overall yield). On a larger scale, Panek's eight-step assembly of the target molecule from the two partners was also slightly modified, giving 45 mg reblastatin (19% overall yield) in the first batch synthesis. Notable feature of our study is the settlement of the C14 chirality through a diastereoselective alpha-alkylation of 6 followed by a three-step full reduction of the lactone carboxyl, making vastly available 6 a universally applicable C11-C14 synthon for benzenoid/benzoquinone ansamycins. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2014.03.020
• 作为产物：
  描述：

  (2RS,5S)-5-<<<(1,1-dimethylethyl)dimethylsilyl>oxy>methyl>tetrahydrofuran-2-ol 在 2,6-二甲基吡啶 、 盐酸 、 lithium hydroxide 、 Schwartz's reagent 、 草酰氯 、 4 A molecular sieve 、 Proton-Sponge 、 二甲基亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 甲苯 、 苯 为溶剂， 反应 67.0h， 生成 (2E,6S,7S,8E,10S,11R,12S,14R)-15-(3-(benzyloxy)-5-bromo-2-methoxyphenyl)-7-((tert-butyldimethylsilyl)oxy)-6,12-dimethoxy-11-(methoxymethoxy)-2,8,10,14-tetramethylpentadeca-2,8-dienoic acid
  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).