5-O-tert-butyl 6-O-methyl (3aS,6R,6aS)-3-bromo-3a,4,6,6a-tetrahydropyrrolo[3,4-d][1,2]oxazole-5,6-dicarboxylate

• 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,6R,6aS)-3-bromo-3a,4,6,6a-tetrahydropyrrolo[3,4-d][1,2]oxazole-5,6-dicarboxylate
• 化学式: C₁₂H₁₇BrN₂O₅
• 分子量: 349.181
• InChiKey: SXNBDGHKHLZJBU-RNJXMRFFSA-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：

  5-O-tert-butyl 6-O-methyl (3aS,6R,6aS)-3-bromo-3a,4,6,6a-tetrahydropyrrolo[3,4-d][1,2]oxazole-5,6-dicarboxylate 在 盐酸 作用下， 反应 3.0h， 以64%的产率得到(+/-)-(3aS,6R,6aS)-3-bromo-4,5,6,6a-tetrahydro-3aH-pyrrolo[3,4-d]isoxazole-6-carboxylic acid
  参考文献：
  名称：

  Synthesis and biological evaluation of new amino acids structurally related to the antitumor agent acivicin

  摘要：

  A set of racemic conformationally constrained analogues of the antitumor antibiotic acivicin (+)-1 has been prepared through a strategy based on 1,3-dipolar cycloaddition of bromonitrile oxide to suitable dipolarophiles. The bromo analogue (2) of acivicin was also synthesized and tested as a reference compound, together with its stereoisomer 3. The antitumor properties of novel amino acids 4-7 were evaluated in vitro against human tumor cell lines. Their efficacy to inhibit glutamate synthase (GltS) from Azospirillum brasilense was also assayed. None of the studied compounds, but 2, showed significant activity.

  DOI：

  10.1016/s0014-827x(03)00107-1
• 作为产物：
  描述：

  1,1-二溴甲醛肟 、 1-tert-butyl 2-methyl 1H-pyrrole-1,2(2H,5H)-dicarboxylate 在 碳酸氢钠 作用下， 以 乙酸乙酯 为溶剂， 反应 144.0h， 以26.5%的产率得到5-O-tert-butyl 6-O-methyl (3aR,6R,6aR)-3-bromo-3a,4,6,6a-tetrahydropyrrolo[3,4-d][1,2]oxazole-5,6-dicarboxylate
  参考文献：
  名称：

  Synthesis of new bicyclic analogues of glutamic acid

  摘要：

  Regioisomeric 3-hydroxyisoxazolinyl prolines [HIP-A (+/-)-6 and HIP-B (+/-)-7], which represent a restricted conformation of NMDA, AMPA, and kainic acid, potent and selective agonists at ionotropic glutamate receptors, have been prepared through two different strategies. In the first approach bromonitrile oxide was added to N-BOC-Delta(3)-pyrroline or N-BOC-Delta(3)-pyrrolin-2-one and the carboxylic group was subsequently appended. The alternative strategy is based on the cycloaddition of the same 1,3-dipole to NBOC-3,3-didehydroproline methyl ester, (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(99)00228-8

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.
• Synthesis and biological evaluation of new amino acids structurally related to the antitumor agent acivicin
  作者：Paola Conti、Gabriella Roda、Helena Stabile、Maria Antonietta Vanoni、Bruno Curti、Marco De Amici

  DOI：10.1016/s0014-827x(03)00107-1

  日期：2003.9

  A set of racemic conformationally constrained analogues of the antitumor antibiotic acivicin (+)-1 has been prepared through a strategy based on 1,3-dipolar cycloaddition of bromonitrile oxide to suitable dipolarophiles. The bromo analogue (2) of acivicin was also synthesized and tested as a reference compound, together with its stereoisomer 3. The antitumor properties of novel amino acids 4-7 were evaluated in vitro against human tumor cell lines. Their efficacy to inhibit glutamate synthase (GltS) from Azospirillum brasilense was also assayed. None of the studied compounds, but 2, showed significant activity.
• Synthesis of new bicyclic analogues of glutamic acid
  作者：Paola Conti、Clelia Dallanoce、Marco De Amici、Carlo De Micheli、Roberta Fruttero

  DOI：10.1016/s0040-4020(99)00228-8

  日期：1999.4

  Regioisomeric 3-hydroxyisoxazolinyl prolines [HIP-A (+/-)-6 and HIP-B (+/-)-7], which represent a restricted conformation of NMDA, AMPA, and kainic acid, potent and selective agonists at ionotropic glutamate receptors, have been prepared through two different strategies. In the first approach bromonitrile oxide was added to N-BOC-Delta(3)-pyrroline or N-BOC-Delta(3)-pyrrolin-2-one and the carboxylic group was subsequently appended. The alternative strategy is based on the cycloaddition of the same 1,3-dipole to NBOC-3,3-didehydroproline methyl ester, (C) 1999 Elsevier Science Ltd. All rights reserved.