3-(2,4-bis(benzyloxy)-6-hydroxyphenyl)-1-phenylpropane-1,2-diol | 1448791-55-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: 3-(2,4-bis(benzyloxy)-6-hydroxyphenyl)-1-phenylpropane-1,2-diol
• 英文别名: 3-[2-Hydroxy-4,6-bis(phenylmethoxy)phenyl]-1-phenylpropane-1,2-diol
• CAS: 1448791-55-6
• 化学式: C₂₉H₂₈O₅
• 分子量: 456.538
• InChiKey: KAVXMVNOXCBWDF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 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)-1-phenylpropane-1,2-diol 在 甲醇 、 三乙基硅烷 、 4-二甲氨基吡啶 、 三氟化硼乙醚 、 palladium diacetate 、 4-甲基苯磺酸吡啶 、 L-Selectride 、 potassium carbonate 、 戴斯-马丁氧化剂 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 lithium bromide 作用下， 以 二氯甲烷 为溶剂， 反应 27.75h， 生成 5,7-dihydroxy-2-phenylchroman-3-yl 4-acetoxy-3-(3-methylbut-2-en-1-yl)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：

  3-苯基丙-2-烯-1-醇 在 硫酸 、 silica gel 、 N-甲基吗啉氧化物 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 18.25h， 生成 3-(2,4-bis(benzyloxy)-6-hydroxyphenyl)-1-phenylpropane-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

• [EN] (-)-EPIGALLOCATECHIN GALLATE DERIVATIVES FOR INHIBITING PROTEASOME<br/>[FR] DERIVES (-)-EPIGALLOCATECHINE GALLATES POUR INHIBER LE PROTEASOME
  申请人：UNIV HONG KONG POLYTECHNIC

  公开号：WO2006017981A1

  公开（公告）日：2006-02-23

  (-)-EGCG, the most abundant catechin, was found to be chemopreventive and anticancer agent. However, (-)-EGCG has at least one limitation: it gives poor bioavailability. This invention provides compounds of generally formulae below, wherein R11, R12, R13, R21, R22, R2, R3, and R4 are each independently selected from the group consisting of -H, and C1 to C10 acyloxyl group; and R5 is selected from the group consisting of -H, C1 -C10 -alkyl, C2 -C10 -alkenyl, C2 -C10 -alkynyl, C3 -C7 -cycloalkyl, phenyl, benzyl and C3 -C7 -cycloalkenyl, whereas each of the last mentioned 7 groups can be substituted with any combination of one to six halogen atoms; at least one of R11, R12, R13, R21, R22, R2, R3 and R4 is -H, which were found to be more potent than their non-protected counterparts, which can be used as proteasome inhibitors to reduce tumor cell growth.

  (-)-EGCG 是最丰富的儿茶素，被发现具有化学预防和抗癌作用。然而，(-)-EGCG 至少存在一个限制：其生物利用度较低。本发明提供了以下一般公式的化合物，其中 R11、R12、R13、R21、R22、R2、R3 和 R4 分别独立地从以下基团中选择：-H 和 C1 至 C10 酰氧基；R5 从以下基团中选择：-H、C1-C10 烷基、C2-C10 烯基、C2-C10 炔基、C3-C7 环烷基、苯基、苄基和 C3-C7 环烯基，而最后提到的 7 个基团中的每一个均可被 1 至 6 个卤素原子的任意组合取代；R11、R12、R13、R21、R22、R2、R3 和 R4 中至少有一个是 -H，这些化合物被发现比其非保护形式的对应物更有效，可用作蛋白酶体抑制剂以减少肿瘤细胞生长。
• EP1778663A4
  申请人：——

  公开号：EP1778663A4

  公开（公告）日：2008-08-06
• (-)-EPIGALLOCATECHIN GALLATE DERIVATIVES FOR INHIBITING PROTEASOME
  申请人：The Hong Kong Polytechnic University

  公开号：EP1778663A1

  公开（公告）日：2007-05-02