(2S,3R,4S,5R,6S)-6-((5,7-bis(benzyloxy)-2-(4-(benzyloxy)phenyl)-4-oxo-4H-chromen-3-yl)oxy)-4,5-dihydroxy-2-propyltetrahydro-2H-pyran-3-yl acetate | 1417412-08-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: (2S,3R,4S,5R,6S)-6-((5,7-bis(benzyloxy)-2-(4-(benzyloxy)phenyl)-4-oxo-4H-chromen-3-yl)oxy)-4,5-dihydroxy-2-propyltetrahydro-2H-pyran-3-yl acetate
• CAS: 1417412-08-8
• 化学式: C₄₆H₄₄O₁₁
• 分子量: 772.849
• InChiKey: KSIRYHZNEJVJAL-NCXMZQOLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.75
• 重原子数：
  57.0
• 可旋转键数：
  15.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  143.12
• 氢给体数：
  2.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  (2S,3R,4S,5R,6S)-6-((5,7-bis(benzyloxy)-2-(4-(benzyloxy)phenyl)-4-oxo-4H-chromen-3-yl)oxy)-4,5-dihydroxy-2-propyltetrahydro-2H-pyran-3-yl acetate 在 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 、 乙醇 为溶剂， -90.0~20.0 ℃ 、101.33 kPa 条件下， 反应 3.0h， 生成 (2S,3R,4S,5R,6S)-6-((5,7-dihydroxy-2-(4-hydroxyphenyl)-4-oxo-4H-chromen-3-yl)oxy)-4,5-dihydroxy-2-propyltetrahydro-2H-pyran-3-yl acetate
  参考文献：
  名称：

  Improving the Affinity of SL0101 for RSK Using Structure-Based Design

  摘要：

  Enhanced activity of the Ser/Thr protein kinase, RSK, is associated with transformation and metastasis, which suggests that RSK is an attractive drug target. The natural product SL0101 (kaempferol 3-O-(3 '',4 ''-di-O-acetyl-alpha-L-rhamnopyranoside)) has been shown to be an RSK selective inhibitor. However, the K-i for SL0101 is 1 mu M with a half-life of less than 30 min in vivo. To identify analogues with improved efficacy we designed a set of analogues based on the crystallographic model of SL0101 in complex with the RSK2 N-terminal kinase domain. We identified an analogue with a 5 ''-n-propyl group on the rhamnose that has >40-fold improved affinity for RSK relative to SL0101 in an in vitro kinase assay. This analogue preferentially inhibited the proliferation of the human breast cancer line, MCF-7, versus the normal untransformed breast line, MCF-10A, which is consistent with results using SL0101. However, the efficacy of the 5 ''-n-propyl analogue to inhibit MCF-7 proliferation was only 2-fold better than for SL0101, which we hypothesize is due to limited membrane permeability. The improved affinity of the 5 ''-n-propyl analogue for RSK will aid in the design of future compounds for in vivo use.

  DOI：

  10.1021/ml300298v
• 作为产物：
  描述：

  在 四氧化锇 、 水 、 N-甲基吗啉氧化物 作用下， 以 丙酮 、 叔丁醇 为溶剂， 反应 8.0h， 生成 (2S,3R,4S,5R,6S)-6-((5,7-bis(benzyloxy)-2-(4-(benzyloxy)phenyl)-4-oxo-4H-chromen-3-yl)oxy)-4,5-dihydroxy-2-propyltetrahydro-2H-pyran-3-yl acetate
  参考文献：
  名称：

  SL0101的C-4''氨基甲酸酯，C-6''n-Pr取代的环醇类似物的区域选择性合成。

  摘要：

  已经实现了SL0101（1）的两个类似物的不对称合成。这项工作旨在发现具有改善的生物利用度的p90核糖体S6激酶（RSK）抑制剂。该路线依赖于使用泰勒催化剂来区域选择性地安装C-3''乙酰基或氨基甲酸酯官能团。这项研究导致鉴定出具有C-4“ n-Pr-氨基甲酸酯和具有改善的RSK抑制活性的C-3”乙酸酯的SL0101第三代类似物。

  DOI：

  10.1021/acs.orglett.0c00042