(E)-2-(4aR,5aS,6S,8aR,8bR)-7-((R)-2-acetoxy-1-(4-methoxyphenyl)ethyl)-6-(benzyl(tert-butoxycarbamoyl)-1-((2-nitrophenyl)sulfonyl)-8-oxo-2,4a,5a,6,7,8,8a,8b-octahydro-1H-pyrrolo[3',4':4,5]furo[3,2-b]pyridin-5a-yl)vinyl acetate | 1427207-93-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (E)-2-(4aR,5aS,6S,8aR,8bR)-7-((R)-2-acetoxy-1-(4-methoxyphenyl)ethyl)-6-(benzyl(tert-butoxycarbamoyl)-1-((2-nitrophenyl)sulfonyl)-8-oxo-2,4a,5a,6,7,8,8a,8b-octahydro-1H-pyrrolo[3',4':4,5]furo[3,2-b]pyridin-5a-yl)vinyl acetate
• CAS: 1427207-93-9
• 化学式: C₄₃H₄₆N₄O₁₄S
• 分子量: 874.923
• InChiKey: INVJAYFMGJXMAS-GYKVQLSZSA-N

反应信息

• 作为产物：
  描述：

  二碳酸二叔丁酯 、 2-((4aR,5aS,6S,8aR,8bR)-7-((R)-2-Acetoxy-1-(4-methoxyphenyl)ethyl)-6-(benzylcarbamoyl)-1-((2-nitrophenyl)sulfonyl)-8-oxo-2,4a,5a,6,7,8,8a,8b-octahydro-1H-pyrrolo[3',4':4,5]furo[3,2-b]pyridin-5a-yl)vinyl acetate 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 生成 (E)-2-(4aR,5aS,6S,8aR,8bR)-7-((R)-2-acetoxy-1-(4-methoxyphenyl)ethyl)-6-(benzyl(tert-butoxycarbamoyl)-1-((2-nitrophenyl)sulfonyl)-8-oxo-2,4a,5a,6,7,8,8a,8b-octahydro-1H-pyrrolo[3',4':4,5]furo[3,2-b]pyridin-5a-yl)vinyl acetate 、 (Z)-2-(4aR,5aS,6S,8aR,8bR)-7-((R)-2-acetoxy-1-(4-methoxyphenyl)ethyl)-6-(benzyl(tert-butoxycarbamoyl)-1-((2-nitrophenyl)sulfonyl)-8-oxo-2,4a,5a,6,7,8,8a,8b-octahydro-1H-pyrrolo[3',4':4,5]furo[3,2-b]pyridin-5a-yl)vinyl acetate
  参考文献：
  名称：

  Studies on an (S)-2-Amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic Acid (AMPA) Receptor Antagonist IKM-159: Asymmetric Synthesis, Neuroactivity, and Structural Characterization

  摘要：

  IKM-159 was developed and identified as a member of a new class of heterotricyclic glutamate analogues that act as AMPA receptor-selective antagonists. However, it was not known which enantiomer of IKM-159 was responsible for its pharmacological activities. Here, we report in vivo and in vitro neuronal activities of both enantiomers of IKM-159 prepared by enantioselective asymmetric synthesis. By employment of (R)-2-amino-2-(4-methoxyphenyl)ethanol as a chiral auxiliary, (2R)-IKM-159 and the (2S)-counterpart were successfully synthesized in 0.70% and 1.5% yields, respectively, over a total of 18 steps. Both behavioral and electrophysiological assays showed that the biological activity observed for the racemic mixture was reproduced only with (2R)-IKM-159, whereas the (2S)-counterpart was inactive in both assays. Racemic IKM-159 was crystallized with the ligand-binding domain of GluA2, and the structure revealed a complex containing (2R)-IKM-159 at the glutamate binding site. (2R)-IKM-159 locks the GluA2 in an open form, consistent with a pharmacological action as competitive antagonist of AMPA receptors.

  DOI：

  10.1021/jm301590z