5-O-tert-butyl 6-O-methyl (3aS,6S,6aS)-3-bromo-3a,4,6,6a-tetrahydropyrrolo[3,4-d][1,2]oxazole-5,6-dicarboxylate | 669071-04-9

• 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: 5-O-tert-butyl 6-O-methyl (3aS,6S,6aS)-3-bromo-3a,4,6,6a-tetrahydropyrrolo[3,4-d][1,2]oxazole-5,6-dicarboxylate
• CAS: 669071-04-9
• 化学式: C₁₂H₁₇BrN₂O₅
• 分子量: 349.181
• InChiKey: SXNBDGHKHLZJBU-FXQIFTODSA-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

文献信息

• Synthesis of enantiomerically pure HIP-A and HIP-B and investigation of their activity as inhibitors of excitatory amino acid transporters
  作者：Andrea Pinto、Paola Conti、Marco De Amici、Lucia Tamborini、Giovanni Grazioso、Simona Colleoni、Tiziana Mennini、Marco Gobbi、Carlo De Micheli

  DOI：10.1016/j.tetasy.2008.03.001

  日期：2008.4

  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.