(3aα,4β,7β,7aα)-2-(2,3,3a,4,7,7a-hexahydro-4,7-methano-1H-inden-2-ylidene)-3,3-dimethyl-1,5-dioxaspiro[5.5]undecane | 319915-24-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (3aα,4β,7β,7aα)-2-(2,3,3a,4,7,7a-hexahydro-4,7-methano-1H-inden-2-ylidene)-3,3-dimethyl-1,5-dioxaspiro[5.5]undecane
• 英文别名: 3,3-dimethyl-9-[(1R,2R,6S,7S)-4-tricyclo[5.2.1.02,6]dec-8-enylidene]-1,5-dioxaspiro[5.5]undecane
• CAS: 319915-24-7；216760-28-0
• 化学式: C₂₁H₃₀O₂
• 分子量: 314.468
• InChiKey: MBPXMBNYBGIWFN-XHVUQVIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  23
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (3aα,4β,7β,7aα)-2-(2,3,3a,4,7,7a-hexahydro-4,7-methano-1H-inden-2-ylidene)-3,3-dimethyl-1,5-dioxaspiro[5.5]undecane 在 (R)-(-)-diisopinocampheylborane 、 pyridinium chlorochromate 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 26.0h， 生成 [3aR(3aα,4β,7β,7aα)]-2-(3,3-dimethyl-1,5-dioxaspiro[5.5]undecan-9-ylidene)perhydro-4,7-methanoinden-5-one
  参考文献：
  名称：

  Chiral Derivatives of 2-Cyclohexylideneperhydro-4,7-methanoindenes, a Novel Class of Nonsteroidal Androgen Receptor Ligand:  Synthesis, X-ray Analysis, and Biological Activity

  摘要：

  A series of 2 -cyclohexylideneperhydro-4,7-methanoindene derivatives was synthesized as novel androgen receptor ligands. Asymmetric hydroboration of Ley intermediate 2 afforded single enantiomer alcohol derivatives (3aR)-3 and (3aS)-3 which could be further transformed to give 12 variously substituted keto alcohol target compounds. X-ray crystallography of the 4-bromo-benzenesulfonyl ester (3aS)-13 was used to establish their absolute configuration. The binding of these compounds to the rat ventral prostate androgen receptor showed moderate affinity with IC50 values of 1.2 muM and above but with substantial enantiomeric dependencies which varied in accordance to Pfieffer's rule. Surprisingly, the (3aS)-5 alpha -alcohols displayed similar affinity to the (3aR)-5 beta -alcohols, and molecular modeling suggested an alternative mode of binding for the (3aS) series. The three compounds with the best androgen receptor affinity were assayed in vivo for antiandrogenic and androgenic effects on sex accessory organ growth in castrated immature rats and were found to be ineffective.

  DOI：

  10.1021/jm0000968
• 作为产物：
  描述：

  3,3-二甲基-1,5-二氧杂螺[5.5]十一烷-9-酮 在 吡啶 、 苯磺酰氯 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 41.5h， 生成 (3aα,4β,7β,7aα)-2-(2,3,3a,4,7,7a-hexahydro-4,7-methano-1H-inden-2-ylidene)-3,3-dimethyl-1,5-dioxaspiro[5.5]undecane
  参考文献：
  名称：

  Burden, Peter M.; Allan, Robin D.; Hambley, Trevor, Journal of the Chemical Society. Perkin transactions I, 1998, # 19, p. 3163 - 3169

  摘要：

  DOI：

文献信息

• Chiral Derivatives of 2-Cyclohexylideneperhydro-4,7-methanoindenes, a Novel Class of Nonsteroidal Androgen Receptor Ligand:  Synthesis, X-ray Analysis, and Biological Activity
  作者：Peter M. Burden、Tu Hoa Ai、Hui Qiang Lin、Mualla Akinci、Michelle Costandi、Trevor M. Hambley、Graham A. R. Johnston

  DOI：10.1021/jm0000968

  日期：2000.11.1

  A series of 2 -cyclohexylideneperhydro-4,7-methanoindene derivatives was synthesized as novel androgen receptor ligands. Asymmetric hydroboration of Ley intermediate 2 afforded single enantiomer alcohol derivatives (3aR)-3 and (3aS)-3 which could be further transformed to give 12 variously substituted keto alcohol target compounds. X-ray crystallography of the 4-bromo-benzenesulfonyl ester (3aS)-13 was used to establish their absolute configuration. The binding of these compounds to the rat ventral prostate androgen receptor showed moderate affinity with IC50 values of 1.2 muM and above but with substantial enantiomeric dependencies which varied in accordance to Pfieffer's rule. Surprisingly, the (3aS)-5 alpha -alcohols displayed similar affinity to the (3aR)-5 beta -alcohols, and molecular modeling suggested an alternative mode of binding for the (3aS) series. The three compounds with the best androgen receptor affinity were assayed in vivo for antiandrogenic and androgenic effects on sex accessory organ growth in castrated immature rats and were found to be ineffective.
• Burden, Peter M.; Allan, Robin D.; Hambley, Trevor, Journal of the Chemical Society. Perkin transactions I, 1998, # 19, p. 3163 - 3169
  作者：Burden, Peter M.、Allan, Robin D.、Hambley, Trevor、Johnston, Graham A. R.

  DOI：——

  日期：——