(2R,3R,4aR,10aR)-7-[tert-butyl(dimethyl)silyl]oxy-4a-ethyl-2-phenyl-1,3,4,9,10,10a-hexahydrophenanthrene-2,3-diol | 1132656-45-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 萘并呋喃类
• 英文名称: (2R,3R,4aR,10aR)-7-[tert-butyl(dimethyl)silyl]oxy-4a-ethyl-2-phenyl-1,3,4,9,10,10a-hexahydrophenanthrene-2,3-diol
• CAS: 1132656-45-1
• 化学式: C₂₈H₄₀O₃Si
• 分子量: 452.709
• InChiKey: PNXMTGMNZOTWAD-OCZKJHHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.32
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  49.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2R,3R,4aR,10aR)-7-[tert-butyl(dimethyl)silyl]oxy-4a-ethyl-2-phenyl-1,3,4,9,10,10a-hexahydrophenanthrene-2,3-diol 在 四丁基氟化铵 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以76%的产率得到(2R,3R,4aR,10aR)-4a-ethyl-2-phenyl-1,2,3,4,4a,9,10,10a-octahydrophenanthrene-2,3,7-triol
  参考文献：
  名称：

  Octahydrophenanthrene-2,7-diol Analogues as Dissociated Glucocorticoid Receptor Agonists: Discovery and Lead Exploration

  摘要：

  As exemplified by the lead compound 2, octahydrophenanthrene-2,7-diol analogues exhibit the profile of a pathway-selective or "dissociated" agonist of the glucocorticoid receptor (GR), retaining the potent activity that glucocorticoids have for transrepression (as measured by inhibition of IL-1 induced MMP-13 expression) but showing an attenuated capacity for transactivation (as measured in an MMTV luciferase reporter assay). With the guidance of a homology model of the GR ligand binding domain, structural modifications to 2 were carried out that were successful in replacing the allyl and propynyl side chains with groups likely to be more chemically stable and less likely to produce toxic metabolites. Key to success was the introduction of an additional hydroxyl group onto the tricyclic carbon framework of the series.

  DOI：

  10.1021/jm801512v
• 作为产物：
  描述：

  (2S,4aS,10aR)-7-(tert-butyldimethylsilanyloxy)-4a-ethyl-2-phenyl-1,2,4a,9,10,10a-hexahydro-1H-phenanthren-2-ol 在 硼烷四氢呋喃络合物 、 双氧水 、 sodium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 以12%的产率得到(2R,3R,4aR,10aR)-7-[tert-butyl(dimethyl)silyl]oxy-4a-ethyl-2-phenyl-1,3,4,9,10,10a-hexahydrophenanthrene-2,3-diol
  参考文献：
  名称：

  Octahydrophenanthrene-2,7-diol Analogues as Dissociated Glucocorticoid Receptor Agonists: Discovery and Lead Exploration

  摘要：

  As exemplified by the lead compound 2, octahydrophenanthrene-2,7-diol analogues exhibit the profile of a pathway-selective or "dissociated" agonist of the glucocorticoid receptor (GR), retaining the potent activity that glucocorticoids have for transrepression (as measured by inhibition of IL-1 induced MMP-13 expression) but showing an attenuated capacity for transactivation (as measured in an MMTV luciferase reporter assay). With the guidance of a homology model of the GR ligand binding domain, structural modifications to 2 were carried out that were successful in replacing the allyl and propynyl side chains with groups likely to be more chemically stable and less likely to produce toxic metabolites. Key to success was the introduction of an additional hydroxyl group onto the tricyclic carbon framework of the series.

  DOI：

  10.1021/jm801512v