(2S,4S)-1-(tert-butoxycarbonyl)-4-bromoproline benzyl ester | 874162-95-5

• 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: (2S,4S)-1-(tert-butoxycarbonyl)-4-bromoproline benzyl ester
• 英文别名: (2S, 4S)-1-N-Boc-4-bromo-proline benzyl ester；2-O-benzyl 1-O-tert-butyl (2S,4S)-4-bromopyrrolidine-1,2-dicarboxylate
• CAS: 874162-95-5
• 化学式: C₁₇H₂₂BrNO₄
• 分子量: 384.27
• InChiKey: BZRCQFJSGVBVKN-KBPBESRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S,4S)-1-(tert-butoxycarbonyl)-4-bromoproline benzyl ester 在 palladium on activated charcoal sodium hydroxide 、 sodium azide 、 氢气 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 55.0 ℃ 、517.11 kPa 条件下， 反应 28.0h， 生成 (2S,4R)-1-(tert-butoxycarbonyl)-4-(N-benzyloxycarbonyl)aminoproline
  参考文献：
  名称：

  Design and Synthesis of Photoaffinity-Labeling Ligands of the l-Prolyl-l-leucylglycinamide Binding Site Involved in the Allosteric Modulation of the Dopamine Receptor

  摘要：

  Pro-Leu-Gly-NH2 (PLG), in addition to its endocrine effects, possesses the ability to modulate dopamine D-2 receptors within the central nervous system. However, the precise binding site of PLG is unknown. Potential photoaffinity-labeling ligands of the PLG binding site were designed as tools to be used in the identification of the macromolecule that possesses this binding site. Six different photoaffinity-labeling ligands were designed and synthesized on the basis of the gamma-lactam PLG peptidomimetic 1. The 4-azidobenzoyl and 4-azido-2-hydroxybenzoyl photoaffinity-labeling moieties were placed at opposite ends of PLG peptidomimetic I to generate a series of ligands that potentially could be used to map the PLG binding site. All of the compounds that were synthesized possessed activity comparable to or better than PLG in enhancing [H-3]-N-propylnorapomorphine agonist binding to dopamine receptors. Photoaffinity ligands that were crosslinked to the receptor preparation produced a modulatory effect that was either comparable to or greater than the increase in agonist binding produced by the respective ligands that were not cross-linked to the dopamine receptor. The results indicate that these photoaffinity-labeling agents are binding at the same allosteric site as PLG and PLG peptidomimetic 1.

  DOI：

  10.1021/jm050644n
• 作为产物：
  描述：

  N-(叔丁氧羰基)-4-羟基脯氨酸苄酯 在 四溴化碳 、 1,2-双(二苯基膦)乙烷 作用下， 以 四氢呋喃 为溶剂， 反应 20.0h， 以84%的产率得到(2S,4S)-1-(tert-butoxycarbonyl)-4-bromoproline benzyl ester
  参考文献：
  名称：

  Discovery of Subnanomolar Arginine-Glycine-Aspartate-Based α_Vβ₃/α_Vβ₅ Integrin Binders Embedding 4-Aminoproline Residues

  摘要：

  The embodiment of 4-aminoproline residues (Amp) into the arginine-glycine-aspartate (RGD) sequence led to the discovery of a novel class of high-affinity alpha v beta(3)/alpha v beta(5) integrin binders [IC50h(alpha v beta(3)) 0.03-5.12 nM; IC50h(alpha v beta(5)) 0.88-154 nM]. A total of eight cyclopeptides of type cyclo-[-Arg-Gly-Asp-Amp-], 5-12, were assembled by a standard solid-phase peptide synthesis protocol that involved the C2-carboxyl and C4-amino functionalities of the proline scaffolds, leaving the N-alpha-nuclear site untouched. Functionalization of this vacant proline site with either alkyl or acyl substituents proved feasible, with significant benefit to the integrin binding capabilities of the ligands. Notably, six out of eight cyclopeptide inhibitors, 5-7 and 9-11, showed moderate yet significant selectivity toward the alpha v beta(3) receptor. The three-dimensional structure in water was determined by NMR techniques and molecular dynamics calculations. Docking studies to the X-ray crystal structure of the extracellular segment of integrin alpha v beta(3) complexed with reference compound 1 were also performed on selected analogues to highlight the structural features required for potent ligand binding affinity.

  DOI：

  10.1021/jm701214z

文献信息

• Discovery of Subnanomolar Arginine-Glycine-Aspartate-Based α_Vβ₃/α_Vβ₅ Integrin Binders Embedding 4-Aminoproline Residues
  作者：Franca Zanardi、Paola Burreddu、Gloria Rassu、Luciana Auzzas、Lucia Battistini、Claudio Curti、Andrea Sartori、Giuseppe Nicastro、Gloria Menchi、Nicoletta Cini、Anna Bottonocetti、Silvia Raspanti、Giovanni Casiraghi

  DOI：10.1021/jm701214z

  日期：2008.3.1

  The embodiment of 4-aminoproline residues (Amp) into the arginine-glycine-aspartate (RGD) sequence led to the discovery of a novel class of high-affinity alpha v beta(3)/alpha v beta(5) integrin binders [IC50h(alpha v beta(3)) 0.03-5.12 nM; IC50h(alpha v beta(5)) 0.88-154 nM]. A total of eight cyclopeptides of type cyclo-[-Arg-Gly-Asp-Amp-], 5-12, were assembled by a standard solid-phase peptide synthesis protocol that involved the C2-carboxyl and C4-amino functionalities of the proline scaffolds, leaving the N-alpha-nuclear site untouched. Functionalization of this vacant proline site with either alkyl or acyl substituents proved feasible, with significant benefit to the integrin binding capabilities of the ligands. Notably, six out of eight cyclopeptide inhibitors, 5-7 and 9-11, showed moderate yet significant selectivity toward the alpha v beta(3) receptor. The three-dimensional structure in water was determined by NMR techniques and molecular dynamics calculations. Docking studies to the X-ray crystal structure of the extracellular segment of integrin alpha v beta(3) complexed with reference compound 1 were also performed on selected analogues to highlight the structural features required for potent ligand binding affinity.
• Design and Synthesis of Photoaffinity-Labeling Ligands of the <scp>l</scp>-Prolyl-<scp>l</scp>-leucylglycinamide Binding Site Involved in the Allosteric Modulation of the Dopamine Receptor
  作者：Abigail Fisher、Amandeep Mann、Vaneeta Verma、Nancy Thomas、Ram K. Mishra、Rodney L. Johnson

  DOI：10.1021/jm050644n

  日期：2006.1.1

  Pro-Leu-Gly-NH2 (PLG), in addition to its endocrine effects, possesses the ability to modulate dopamine D-2 receptors within the central nervous system. However, the precise binding site of PLG is unknown. Potential photoaffinity-labeling ligands of the PLG binding site were designed as tools to be used in the identification of the macromolecule that possesses this binding site. Six different photoaffinity-labeling ligands were designed and synthesized on the basis of the gamma-lactam PLG peptidomimetic 1. The 4-azidobenzoyl and 4-azido-2-hydroxybenzoyl photoaffinity-labeling moieties were placed at opposite ends of PLG peptidomimetic I to generate a series of ligands that potentially could be used to map the PLG binding site. All of the compounds that were synthesized possessed activity comparable to or better than PLG in enhancing [H-3]-N-propylnorapomorphine agonist binding to dopamine receptors. Photoaffinity ligands that were crosslinked to the receptor preparation produced a modulatory effect that was either comparable to or greater than the increase in agonist binding produced by the respective ligands that were not cross-linked to the dopamine receptor. The results indicate that these photoaffinity-labeling agents are binding at the same allosteric site as PLG and PLG peptidomimetic 1.