(-)-(3aR,6S,6aR)-3-bromo-5-tert-butoxycarbonyl-6-methoxycarbonyl-3a,4,6,6a-tetrahydro-pyrrolo[3,4-d]isoxazole | 1037237-79-8

• 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: (-)-(3aR,6S,6aR)-3-bromo-5-tert-butoxycarbonyl-6-methoxycarbonyl-3a,4,6,6a-tetrahydro-pyrrolo[3,4-d]isoxazole
• 英文别名: 5-O-tert-butyl 6-O-methyl (3aR,6S,6aR)-3-bromo-3a,4,6,6a-tetrahydropyrrolo[3,4-d][1,2]oxazole-5,6-dicarboxylate
• CAS: 1037237-79-8
• 化学式: C₁₂H₁₇BrN₂O₅
• 分子量: 349.181
• InChiKey: SXNBDGHKHLZJBU-GJMOJQLCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  77.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (-)-(3aR,6S,6aR)-3-bromo-5-tert-butoxycarbonyl-6-methoxycarbonyl-3a,4,6,6a-tetrahydro-pyrrolo[3,4-d]isoxazole 在 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 3.0h， 以71%的产率得到3-hydroxy-5-tert-butoxycarbonyl-3a,5,6,6a-tetrahydro-4H-pyrrolo[3,4-d]isoxazole-6-carboxylic acid
  参考文献：
  名称：

  Synthesis of enantiomerically pure HIP-A and HIP-B and investigation of their activity as inhibitors of excitatory amino acid transporters

  摘要：

  The present report deals with the synthesis of the two couples of enantiomers (+)-(3aS,4R,6aS)-/(-)-(3aR,4S,6aR)-3-hydroxy-3a,4,6,6a-tetrahydro-pyrrolo[3,4-d]isoxazole-4-carboxylic acid [(+)-HIP-A and (-)-HIP-A] and (+)-(3aS,6S,6aS)-/(-)-(3aR,6R,6aR)3-hydroxy-3a,4,6,6a-tetrahydro-pyrrolo[3,4-d] isoxizole-6-carboxylic acid [(+)-HIP-B and (-)-HIP-B], and the investigation of their inhibitory activity at EAATs. When tested in a [3 H]D-aspartate uptake assay on native EAATs present in rat brain synaptosomal fractions, (-)-HIP-A and (+)-HIP-B turned Out to be considerably more potent than their enantiomers; in particular, (-)-HIP-A showed an eudismic ratio (ER) higher than 100. Molecular modeling investigations gave clues with regard to the key amino acid residues involved in the binding with our inhibitors and provided explanations for the observed stereo selectivity. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2008.03.001
• 作为产物：
  描述：

  1,1-二溴甲醛肟 、 BOC-4-去氢-L-脯氨酸 在 碳酸氢钠 作用下， 以 乙酸乙酯 为溶剂， 反应 144.0h， 以0.91 g的产率得到(-)-(3aR,6S,6aR)-3-bromo-5-tert-butoxycarbonyl-6-methoxycarbonyl-3a,4,6,6a-tetrahydro-pyrrolo[3,4-d]isoxazole
  参考文献：
  名称：

  Synthesis of enantiomerically pure HIP-A and HIP-B and investigation of their activity as inhibitors of excitatory amino acid transporters

  摘要：

  The present report deals with the synthesis of the two couples of enantiomers (+)-(3aS,4R,6aS)-/(-)-(3aR,4S,6aR)-3-hydroxy-3a,4,6,6a-tetrahydro-pyrrolo[3,4-d]isoxazole-4-carboxylic acid [(+)-HIP-A and (-)-HIP-A] and (+)-(3aS,6S,6aS)-/(-)-(3aR,6R,6aR)3-hydroxy-3a,4,6,6a-tetrahydro-pyrrolo[3,4-d] isoxizole-6-carboxylic acid [(+)-HIP-B and (-)-HIP-B], and the investigation of their inhibitory activity at EAATs. When tested in a [3 H]D-aspartate uptake assay on native EAATs present in rat brain synaptosomal fractions, (-)-HIP-A and (+)-HIP-B turned Out to be considerably more potent than their enantiomers; in particular, (-)-HIP-A showed an eudismic ratio (ER) higher than 100. Molecular modeling investigations gave clues with regard to the key amino acid residues involved in the binding with our inhibitors and provided explanations for the observed stereo selectivity. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2008.03.001