3-(2,4-bis(benzyloxy)-6-hydroxyphenyl)propane-1,2-diol | 1448791-92-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-(2,4-bis(benzyloxy)-6-hydroxyphenyl)propane-1,2-diol
• 英文别名: 3-[2-Hydroxy-4,6-bis(phenylmethoxy)phenyl]propane-1,2-diol；3-[2-hydroxy-4,6-bis(phenylmethoxy)phenyl]propane-1,2-diol
• CAS: 1448791-92-1
• 化学式: C₂₃H₂₄O₅
• 分子量: 380.441
• InChiKey: LFECVVPJCSIBEM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  79.2
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(2,4-bis(benzyloxy)-6-hydroxyphenyl)propane-1,2-diol 在 吡啶 、 甲醇 、 4-二甲氨基吡啶 、 potassium carbonate 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 生成 5,7-bis(benzyloxy)chroman-3-yl 3-(benzyloxy)benzoate
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationships of EGCG Analogues, a Recently Identified Hsp90 Inhibitor

  摘要：

  Epigallocatechin-3-gallate (EGCG), the principal polyphenol isolated from green tea, was recently shown to inhibit Hsp90; however, structure activity relationships for this natural product have not yet been produced. Herein, we report the synthesis and biological evaluation of EGCG analogues to establish structure activity relationships between EGCG and Hsp90. All four rings as well as the linker connecting the C- and the D-rings were systematically investigated, which led to the discovery of compounds that inhibit Hs90 and display improvement in efficacy over EGCG. Antiproliferative activity of all the analogues was determined against MCF-7 and SKBr3 cell lines and Hsp90 inhibitory activity of the four most potent analogues was further evaluated by Western blot analyses and degradation of Hsp90-dependent client proteins. The prenyl-substituted aryl ester of 3,5-dihydroxychroman-3-ol ring system was identified as a novel scaffold that exhibits Hsp90 inhibitory activity.

  DOI：

  10.1021/jo401027r
• 作为产物：
  描述：

  (((5-(allyloxy)-1,3-phenylene)bis(oxy))bis(methylene))dibenzene 在 四氧化锇 、 N-甲基吗啉氧化物 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 24.0h， 生成 3-(2,4-bis(benzyloxy)-6-hydroxyphenyl)propane-1,2-diol
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationships of EGCG Analogues, a Recently Identified Hsp90 Inhibitor

  摘要：

  Epigallocatechin-3-gallate (EGCG), the principal polyphenol isolated from green tea, was recently shown to inhibit Hsp90; however, structure activity relationships for this natural product have not yet been produced. Herein, we report the synthesis and biological evaluation of EGCG analogues to establish structure activity relationships between EGCG and Hsp90. All four rings as well as the linker connecting the C- and the D-rings were systematically investigated, which led to the discovery of compounds that inhibit Hs90 and display improvement in efficacy over EGCG. Antiproliferative activity of all the analogues was determined against MCF-7 and SKBr3 cell lines and Hsp90 inhibitory activity of the four most potent analogues was further evaluated by Western blot analyses and degradation of Hsp90-dependent client proteins. The prenyl-substituted aryl ester of 3,5-dihydroxychroman-3-ol ring system was identified as a novel scaffold that exhibits Hsp90 inhibitory activity.

  DOI：

  10.1021/jo401027r

文献信息

• Synthesis and Structure–Activity Relationships of EGCG Analogues, a Recently Identified Hsp90 Inhibitor
  作者：Anuj Khandelwal、Jessica A. Hall、Brian S. J. Blagg

  DOI：10.1021/jo401027r

  日期：2013.8.16

  Epigallocatechin-3-gallate (EGCG), the principal polyphenol isolated from green tea, was recently shown to inhibit Hsp90; however, structure activity relationships for this natural product have not yet been produced. Herein, we report the synthesis and biological evaluation of EGCG analogues to establish structure activity relationships between EGCG and Hsp90. All four rings as well as the linker connecting the C- and the D-rings were systematically investigated, which led to the discovery of compounds that inhibit Hs90 and display improvement in efficacy over EGCG. Antiproliferative activity of all the analogues was determined against MCF-7 and SKBr3 cell lines and Hsp90 inhibitory activity of the four most potent analogues was further evaluated by Western blot analyses and degradation of Hsp90-dependent client proteins. The prenyl-substituted aryl ester of 3,5-dihydroxychroman-3-ol ring system was identified as a novel scaffold that exhibits Hsp90 inhibitory activity.