(1S,2R)-(-)-tert-butyl 1--2-(hydroxymethyl)cyclopropane-1-carboxylate | 143122-76-3

• 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: (1S,2R)-(-)-tert-butyl 1--2-(hydroxymethyl)cyclopropane-1-carboxylate
• 英文别名: tert-butyl (1S,2R)-1-(tert-butoxycarbonylamino)-2-(hydroxymethyl)cyclopropane-1-carboxylate；(1S,2R)-(-)-tert-butyl 1-[N-(tert-butoxycarbonyl)amino]-2-(hydroxymethyl)cyclopropane-1-carboxylate；tert-butyl (1S,2R)-2-(hydroxymethyl)-1-[(2-methylpropan-2-yl)oxycarbonylamino]cyclopropane-1-carboxylate
• CAS: 143122-76-3
• 化学式: C₁₄H₂₅NO₅
• 分子量: 287.356
• InChiKey: XTRFFXDMIUBPNH-XPTSAGLGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (1S,2R)-(-)-tert-butyl 1--2-(hydroxymethyl)cyclopropane-1-carboxylate 在 18-冠醚-6 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 tert-butyl (1S,2S)-2-(cyanomethyl)-1-[(2-methylpropan-2-yl)oxycarbonylamino]cyclopropane-1-carboxylate
  参考文献：
  名称：

  受保护的2,3-甲基谷氨酰胺的立体异构体的不对称合成

  摘要：

  Chirons 1和2，无论是从甘露糖醇，用于制备对映体纯的顺式和反式2,3- methanoglutamine（立体异构体环-谷氨酰胺以适合于固相肽合成被保护的形式）。

  DOI：

  10.1016/0040-4039(95)01659-6
• 作为产物：
  描述：

  (1S,2R)-(-)-tert-butyl 2-(acetoxymethyl)-1-cyclopropane-1-carboxylate 在 甲醇 、 potassium carbonate 作用下， 生成 (1S,2R)-(-)-tert-butyl 1--2-(hydroxymethyl)cyclopropane-1-carboxylate
  参考文献：
  名称：

  Synthesis and Biological Evaluation of 1-Amino-2-Phosphonomethylcyclopropanecarboxylic Acids, New Group III Metabotropic Glutamate Receptor Agonists

  摘要：

  Stereoisomers of 1-amino-2-phosphonomethylcyclopropanecarboxylic acid (APCPr), conformationally restricted analogues of L-AP4 (2-amino-4-phosphonobutyric acid), have been prepared and evaluated at recombinant group III metabotropic glutamate receptors. They activate these receptors over a broad range of potencies. The most potent isomer (1S,2R)-APCPr displays a similar pharmacological profile as that of L-AP4 (EC50 0.72, 1.95, > 500, 0.34 mu M at mGlu4, 6, 7, 8 receptors, respectively, and no effect at group I/II mGluRs). It was characterized on native receptors located in the basal ganglia (BG) where it induced a robust and reversible inhibition of synaptic transmission. It was tested in vivo in haloperidol-induced catalepsy, a model of Parkinsonian akinesia, by direct infusion in the globus pallidus of the BG. At a dose of 0.5 nmol/mu L, catalepsy was significantly antagonized. This study reveals that (1S,2R)-APCPr is a potent group III mGluR agonist and confirms that these receptors may be considered as a therapeutic target in the Parkinson's disease.

  DOI：

  10.1021/jm070262c

文献信息

• Asymmetric syntheses of all four stereoisomers of 2,3-methanomethionine
  作者：Kevin Burgess、Kwok Kan Ho

  DOI：10.1021/jo00048a028

  日期：1992.10

  Asymmetric syntheses of all four stereoisomers of 2,3-methanomethionine ((Z)- and (E)-cyclo-Met) are described. The source of chirality in these reactions is the trifluoromethylsulfonate ester 1b which reacts with di-tert-butyl malonate via direct displacement of trifluoromethylsulfonate followed by lactonization to give 1-(tert-butoxycarbonyl)-2-oxo-3-oxabicyclo[3.1.0]hexane (2). Conversion of compound 2 into (Z)-cyclo-Met can be achieved via ring opening of the lactone, Hoffmann rearrangement, mesylation, and displacement with thiomethoxide. A route to (E)-cyclo-Met was developed using a lipase to effect a critical ester hydrolysis.
• Asymmetric syntheses of the stereoisomers of protected 2,3-methanoglutamine
  作者：Kevin Burgess、Dong Yeol Lim

  DOI：10.1016/0040-4039(95)01659-6

  日期：1995.10

  Chirons 1 and 2, both from mannitol, were used to prepare enantiomerically pure cis and trans stereoisomers of 2,3-methanoglutamine (cyclo-Gln) in a protected form suitable for solid phase peptide synthesis.

  Chirons 1和2，无论是从甘露糖醇，用于制备对映体纯的顺式和反式2,3- methanoglutamine（立体异构体环-谷氨酰胺以适合于固相肽合成被保护的形式）。
• Synthesis and Biological Evaluation of 1-Amino-2-Phosphonomethylcyclopropanecarboxylic Acids, New Group III Metabotropic Glutamate Receptor Agonists
  作者：Pauline Sibille、Sébastien Lopez、Isabelle Brabet、Ornella Valenti、Nadia Oueslati、Florence Gaven、Cyril Goudet、Hugues-Olivier Bertrand、Jacques Neyton、Michael J. Marino、Marianne Amalric、Jean-Philippe Pin、Francine C. Acher

  DOI：10.1021/jm070262c

  日期：2007.7.1

  Stereoisomers of 1-amino-2-phosphonomethylcyclopropanecarboxylic acid (APCPr), conformationally restricted analogues of L-AP4 (2-amino-4-phosphonobutyric acid), have been prepared and evaluated at recombinant group III metabotropic glutamate receptors. They activate these receptors over a broad range of potencies. The most potent isomer (1S,2R)-APCPr displays a similar pharmacological profile as that of L-AP4 (EC50 0.72, 1.95, > 500, 0.34 mu M at mGlu4, 6, 7, 8 receptors, respectively, and no effect at group I/II mGluRs). It was characterized on native receptors located in the basal ganglia (BG) where it induced a robust and reversible inhibition of synaptic transmission. It was tested in vivo in haloperidol-induced catalepsy, a model of Parkinsonian akinesia, by direct infusion in the globus pallidus of the BG. At a dose of 0.5 nmol/mu L, catalepsy was significantly antagonized. This study reveals that (1S,2R)-APCPr is a potent group III mGluR agonist and confirms that these receptors may be considered as a therapeutic target in the Parkinson's disease.