1,1-dimethylethyl {(2S)-1-[(1S,5R)-5,8,8-trimethyl-2-oxo-3-oxabicyclo[3.2.1]octan-1-ylcarbonyl]pyrrolidin-2-yl}acetate | 259868-81-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 1,1-dimethylethyl {(2S)-1-[(1S,5R)-5,8,8-trimethyl-2-oxo-3-oxabicyclo[3.2.1]octan-1-ylcarbonyl]pyrrolidin-2-yl}acetate
• 英文别名: tert-butyl 2-[(2S)-1-[(1S,5R)-5,8,8-trimethyl-2-oxo-3-oxabicyclo[3.2.1]octane-1-carbonyl]pyrrolidin-2-yl]acetate
• CAS: 259868-81-0
• 化学式: C₂₁H₃₃NO₅
• 分子量: 379.497
• InChiKey: BXJBJNPVKSTFBH-WVFSVQOHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  72.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1,1-dimethylethyl {(2S)-1-[(1S,5R)-5,8,8-trimethyl-2-oxo-3-oxabicyclo[3.2.1]octan-1-ylcarbonyl]pyrrolidin-2-yl}acetate 在 盐酸 、 溶剂黄146 作用下， 反应 24.0h， 以71%的产率得到(S)-2-(pyrrolidin-2-yl)acetic acid hydrochloride
  参考文献：
  名称：

  New highly potent GABA uptake inhibitors selective for GAT-1 and GAT-3 derived from (R)- and (S)-proline and homologous pyrrolidine-2-alkanoic acids

  摘要：

  We synthesized proline and pyrrolidine-2-alkanoic acid derivatives in their enantiomerically pure form and evaluated them for their affinity to the GABA transport proteins GAT-1 and GAT-3. Among the compounds presented herein, (R)-pyrrolidine-2-acetic acid (R)-4d substituted with a 2- [tris(4-methoxyphenyl)methoxy] ethyl residue at the nitrogen atom showed the highest affinity at GAT-3 (IC50 = 3.1 mu M) comparable with the well-known GAT-3 blocker (S)-SNAP-5114. Compound (R)-4d displayed excellent subtype selectivity for GAT-3 (GAT-3:GAT-1 = 20:1). (S)-2-pyrrolidineacetic acid derivatives (S)-4b provided with a 4,4-diphenylbut-3-en-1-yl moiety and (S)-4c substituted with a 4,4-[di(3-methylthiophen-2-yl)]phenylbut-3-en-l-yl residue at the nitrogen atom exhibited IC50 values of 0.396 mu M and 0.343 mu M at the GAT-1 protein, respectively. (c) 2006 Elsevier SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2006.01.019
• 作为产物：
  描述：

  (1R,5R)-5,8,8-trimethyl-2-oxo-3-oxabicyclo[3.2.1]octane-1-carbonyl chloride 在 hydridotetakis(triphenylphosphine)rhodium(I) 盐酸 、 三乙胺 作用下， 以 二氯甲烷 、 xylene 为溶剂， 反应 72.33h， 生成 1,1-dimethylethyl {(2S)-1-[(1S,5R)-5,8,8-trimethyl-2-oxo-3-oxabicyclo[3.2.1]octan-1-ylcarbonyl]pyrrolidin-2-yl}acetate
  参考文献：
  名称：

  New highly potent GABA uptake inhibitors selective for GAT-1 and GAT-3 derived from (R)- and (S)-proline and homologous pyrrolidine-2-alkanoic acids

  摘要：

  We synthesized proline and pyrrolidine-2-alkanoic acid derivatives in their enantiomerically pure form and evaluated them for their affinity to the GABA transport proteins GAT-1 and GAT-3. Among the compounds presented herein, (R)-pyrrolidine-2-acetic acid (R)-4d substituted with a 2- [tris(4-methoxyphenyl)methoxy] ethyl residue at the nitrogen atom showed the highest affinity at GAT-3 (IC50 = 3.1 mu M) comparable with the well-known GAT-3 blocker (S)-SNAP-5114. Compound (R)-4d displayed excellent subtype selectivity for GAT-3 (GAT-3:GAT-1 = 20:1). (S)-2-pyrrolidineacetic acid derivatives (S)-4b provided with a 4,4-diphenylbut-3-en-1-yl moiety and (S)-4c substituted with a 4,4-[di(3-methylthiophen-2-yl)]phenylbut-3-en-l-yl residue at the nitrogen atom exhibited IC50 values of 0.396 mu M and 0.343 mu M at the GAT-1 protein, respectively. (c) 2006 Elsevier SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2006.01.019

文献信息

• New highly potent GABA uptake inhibitors selective for GAT-1 and GAT-3 derived from (R)- and (S)-proline and homologous pyrrolidine-2-alkanoic acids
  作者：Günther H. Fülep、Cornelia E. Hoesl、Georg Höfner、Klaus T. Wanner

  DOI：10.1016/j.ejmech.2006.01.019

  日期：2006.7

  We synthesized proline and pyrrolidine-2-alkanoic acid derivatives in their enantiomerically pure form and evaluated them for their affinity to the GABA transport proteins GAT-1 and GAT-3. Among the compounds presented herein, (R)-pyrrolidine-2-acetic acid (R)-4d substituted with a 2- [tris(4-methoxyphenyl)methoxy] ethyl residue at the nitrogen atom showed the highest affinity at GAT-3 (IC50 = 3.1 mu M) comparable with the well-known GAT-3 blocker (S)-SNAP-5114. Compound (R)-4d displayed excellent subtype selectivity for GAT-3 (GAT-3:GAT-1 = 20:1). (S)-2-pyrrolidineacetic acid derivatives (S)-4b provided with a 4,4-diphenylbut-3-en-1-yl moiety and (S)-4c substituted with a 4,4-[di(3-methylthiophen-2-yl)]phenylbut-3-en-l-yl residue at the nitrogen atom exhibited IC50 values of 0.396 mu M and 0.343 mu M at the GAT-1 protein, respectively. (c) 2006 Elsevier SAS. All rights reserved.