2,6-bis(benzyloxy)-4-<(1,1-dimethylethoxy)carbonyl>benzoic acid | 158980-56-4

• 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: 2,6-bis(benzyloxy)-4-<(1,1-dimethylethoxy)carbonyl>benzoic acid
• 英文别名: 2,6-dibenzyloxy-4-(1,1-dimethylethoxycarbonyl)benzoic acid；4-[(2-Methylpropan-2-yl)oxycarbonyl]-2,6-bis(phenylmethoxy)benzoic acid
• CAS: 158980-56-4
• 化学式: C₂₆H₂₆O₆
• 分子量: 434.489
• InChiKey: CAOGIXFMFZTDCK-UHFFFAOYSA-N

物化性质

• 沸点：
  598.8±50.0 °C(predicted)
• 密度：
  1.210±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  32
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  82.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,6-bis(benzyloxy)-4-<(1,1-dimethylethoxy)carbonyl>benzoic acid 在 吡啶 、 喹啉 、 重铬酸吡啶 、 正丁基锂 、 草酰氯 、 四丁基高锰酸胺盐 、 potassium tert-butylate 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-(6-Benzyloxy-2-(benzyloxycarbonyl)benzoyl)-3,5-dibenzyloxybenzoic Acid
  参考文献：
  名称：

  Total Synthesis of (-)-Balanol

  摘要：

  (-)-Balanol是一种具有强效蛋白激酶C抑制活性的真菌 metabolite，我们已通过全合成方法成功制备。该合成方法采用了阴离子同系Fries重排策略来构建苯丙酮（benzophenone）部分，同时将叠氮（azepane）部分由(2S,3R)-3-羟基赖氨酸（3-hydroxylysine）获取。

  DOI：

  10.1021/jo00097a014
• 作为产物：
  描述：

  4-溴-3,5-二羟基苯甲酸 在 sodium hydroxide 、 正丁基锂 、 potassium carbonate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N'-羰基二咪唑 作用下， 生成 2,6-bis(benzyloxy)-4-<(1,1-dimethylethoxy)carbonyl>benzoic acid
  参考文献：
  名称：

  Total Synthesis of (-)-Balanol

  摘要：

  (-)-Balanol是一种具有强效蛋白激酶C抑制活性的真菌 metabolite，我们已通过全合成方法成功制备。该合成方法采用了阴离子同系Fries重排策略来构建苯丙酮（benzophenone）部分，同时将叠氮（azepane）部分由(2S,3R)-3-羟基赖氨酸（3-hydroxylysine）获取。

  DOI：

  10.1021/jo00097a014

文献信息

• Total Synthesis of (-)-Balanol
  作者：John W. Lampe、Philip F. Hughes、Christopher K. Biggers、Shelley H. Smith、Hong Hu

  DOI：10.1021/jo00097a014

  日期：1994.9

  (-)-Balanol, a fungal metabolite with potent protein kinase C inhibitory properties, has been prepared in a total synthesis which makes use of an anionic homo-Fries rearrangement approach to the benzophenone subunit and in which the azepane subunit is obtained from (2S,3R)-3-hydroxylysine.

  (-)-Balanol是一种具有强效蛋白激酶C抑制活性的真菌 metabolite，我们已通过全合成方法成功制备。该合成方法采用了阴离子同系Fries重排策略来构建苯丙酮（benzophenone）部分，同时将叠氮（azepane）部分由(2S,3R)-3-羟基赖氨酸（3-hydroxylysine）获取。
• Synthesis and Protein Kinase Inhibitory Activity of Balanol Analogues with Modified Benzophenone Subunits
  作者：John W. Lampe、Christopher K. Biggers、Jean M. Defauw、Robert J. Foglesong、Steven E. Hall、Julia M. Heerding、Sean P. Hollinshead、Hong Hu、Philip F. Hughes、G. Erik Jagdmann、Mary George Johnson、Yen-Shi Lai、Christopher T. Lowden、Michael P. Lynch、José S. Mendoza、Marcia M. Murphy、Joseph W. Wilson、Lawrence M. Ballas、Kiyomi Carter、James W. Darges、Jefferson E. Davis、Frederick R. Hubbard、Mark L. Stamper

  DOI：10.1021/jm020018f

  日期：2002.6.1

  A series of analogues of the protein kinase C (PKC) inhibitory natural product balanol which bear modified benzophenone subunits are described. The analogues were designed with the goal of uncovering structure - activity features that could be used in the development of PKC inhibitors with a reduced polar character compared to balanol itself. The results of these studies suggest that most of the benzophenone features found in the natural product are important for obtaining potent PKC inhibitory compounds. However, several modifications were found to lead to selective inhibitors of the related enzyme protein kinase A (PKA), and several specific modifications to the polar structural elements of the benzophenone were found to provide potent PKC inhibitors. In particular, it was found that replacement of the benzophenone carboxylate with bioisosteric equivalents could lead to potent analogues. Further, a tolerance for lipophilic substituents on the terminal benzophenone ring was uncovered. These results are discussed in light of recently available structural information for PKA.
• BALANOIDS
  申请人：SPHINX PHARMACEUTICALS CORPORATION

  公开号：EP0687249A1

  公开（公告）日：1995-12-20
• [EN] BALANOIDS<br/>[FR] BALANOIDES
  申请人：——

  公开号：WO1994020062A2

  公开（公告）日：1994-09-15

  [EN] A novel class of therapeutic compounds, denominated Balanoids, is disclosed. Balanoids have protein kinase C inhibitory activity and selectivity among the isoforms of protein kinase C. Balanoids are useful for treatment of diseases related to protein kinase C in animals, especially humans and is especially indicated for treatment of inflammatory diseases.
  [FR] Nouvelle classe de composés thérapeutiques nommés balanoïdes. Lesdits composés possèdent une activité inhibitrice de la protéine kinase C et une sélectivité parmi les isoformes de la protéine kinase C. Les balanoïdes sont utiles pour traiter les maladies liées à la protéine kinase C chez les animaux, en particulier chez leshumains, et ils sont particulièrement indiqués pour traiter les maladies inflammatoires.
• Total Synthesis of (−)- and (+)-Balanol¹
  作者：John W. Lampe、Philip F. Hughes、Christopher K. Biggers、Shelley H. Smith、Hong Hu

  DOI：10.1021/jo952280k

  日期：1996.1.1

  Two total syntheses of the potent protein kinase C inhibitory fungal metabolite balanol are described. In the first approach, the core aminohydroxyazepane subunit was prepared in racemic form by stereospecific functionalization of N-benzyl-epsilon-caprolactam. Resolution prior to coupling to the benzophenone subunit provided access to both enantiomers of balanol. In the second approach, an efficient silicon-mediated cyclization of(2S,3R)-3-hydroxylysine followed by reduction provided the azepane subunit in enantiomerically pure form. The sterically congested benzophenone subunit was assembled from two highly substituted aromatic precursors by way of an anionic home-Fries rearrangement.