3-(benzyloxy)-5-bromo-2-methoxybenzaldehyde | 869732-13-8

• 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: 3-(benzyloxy)-5-bromo-2-methoxybenzaldehyde
• 英文别名: 5-Bromo-2-methoxy-3-phenylmethoxybenzaldehyde
• CAS: 869732-13-8
• 化学式: C₁₅H₁₃BrO₃
• 分子量: 321.17
• InChiKey: ABSMNQTVDDMKED-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(benzyloxy)-5-bromo-2-methoxybenzaldehyde 在 咪唑 、 2,6-二甲基吡啶 、 lead(IV) acetate 、 盐酸 、 三乙基硅烷 、 4-二甲氨基吡啶 、 lithium hydroxide 、 sodium periodate 、 四氧化锇 、 Schwartz's reagent 、 三氟甲磺酸三甲基硅酯 、 dimethyl sulfide borane 、 三氯化硼-甲硫醚 、 4 A molecular sieve 、 三氟化硼乙醚 、 potassium tert-butylate 、 1,8-双二甲氨基萘 、 碳酸氢钠 、 potassium carbonate 、 N-甲基吗啉氧化物 、 N,N-二异丙基乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 丙酮 、 甲苯 、 苯 为溶剂， 反应 145.0h， 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
• 作为产物：
  描述：

  2,3-二羟基苯甲醛 在 溴 、 sodium acetate 、 sodium hydride 、 potassium carbonate 、 溶剂黄146 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 49.5h， 生成 3-(benzyloxy)-5-bromo-2-methoxybenzaldehyde
  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).
• Mild Reductive Opening of Aryl Pyranosides Promoted by Scandium(III) Triflate
  作者：Hua-Li Qin、Jason T. Lowe、James S. Panek

  DOI：10.1021/ja067234o

  日期：2007.1.1
• Total synthesis of reblastatin: convenient preparation of coupling partners and scaled assembly
  作者：Chuancai Bian、Rui Yan、Xiaoming Yu

  DOI：10.1016/j.tet.2014.03.020

  日期：2014.5

  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.
• Total Synthesis of Reblastatin
  作者：Iwona E. Wrona、Ana E. Gabarda、Gwilherm Evano、James S. Panek

  DOI：10.1021/ja055384d

  日期：2005.11.1

  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.