(7-bromo)Trp(Boc)-OtBu | 642073-52-7

• 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: (7-bromo)Trp(Boc)-OtBu
• 英文别名: tert-butyl 3-[(2S)-2-amino-3-[(2-methylpropan-2-yl)oxy]-3-oxopropyl]-7-bromoindole-1-carboxylate
• CAS: 642073-52-7
• 化学式: C₂₀H₂₇BrN₂O₄
• 分子量: 439.349
• InChiKey: QRNSKSFHMLVXMU-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  83.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (7-bromo)Trp(Boc)-OtBu 在 盐酸 、 氯甲酸乙酯 、 三乙胺 作用下， 以 四氢呋喃 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.33h， 生成 Z-(7-bromo)Trp-NHMe
  参考文献：
  名称：

  Linear TMC-95-Based Proteasome Inhibitors

  摘要：

  We have designed and evaluated 45 linear analogues of the natural constrained cyclopeptide TMC-95A. These synthetically less demanding molecules are based on the tripeptide sequence Y-N-W of TMC-95A. Structural variations in the amino acid side chains and termini greatly influenced both the efficiency and selectivity of action on a given type of active site. Inhibition constants were submicromolar (K-i approximate to 300 nM) despite the absence of the entropically favorable constrained conformation that is characteristic of TMC-95A and its cyclic analogues. These linear compounds were readily prepared and reasonably stable in culture medium and could be optimized to inhibit one, two, or all three proteasome catalytic sites. Cytotoxicity assays performed on a series of human tumor cell lines identified the most potent inhibitors in cells.

  DOI：

  10.1021/jm0701324
• 作为产物：
  描述：

  tert-butyl 7-bromo-3-formyl-1H-indole-1-carboxylate 在 cesium hydroxide 、 sodium tetrahydroborate 、 (-)-O-allyl-N-(9-anthracenylmethyl)cinchonidium bromide 、 溴 、 三苯基膦 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 28.75h， 生成 (7-bromo)Trp(Boc)-OtBu
  参考文献：
  名称：

  蛋白酶体抑制剂TMC-95A的大环肽类似物的合成。

  摘要：

  描述了作为潜在的蛋白酶体抑制剂的TMC-95A的三种受限大环肽类似物1的合成。关键步骤涉及Ni（0）介导的三肽2的大环化，该三肽2带有卤化芳族侧链，用于形成联芳基。另外，以良好的总收率和以非常高的ee（＞ 85％）在多克规模上获得了使用甘氨酸二苯甲酮亚胺的Corey-O'Donnell烷基化的1-7-溴色氨酸甲酯3的对映选择性制备。

  DOI：

  10.1021/jo035256c

文献信息

• WO2006/105811
  申请人：——

  公开号：——

  公开（公告）日：——
• Synthesis of Macrocyclic Peptide Analogues of Proteasome Inhibitor TMC-95A
  作者：Alexandra Berthelot、Sandrine Piguel、Gwennaël Le Dour、Joëlle Vidal

  DOI：10.1021/jo035256c

  日期：2003.12.1

  The synthesis of three constrained macrocyclic peptide analogues 1 of TMC-95A as potential proteasome inhibitors is described. The key step involves a Ni(0)-mediated macrocyclization of tripeptides 2 bearing halogenated aromatic side chains for the formation of the biaryl junction. In addition, an enantioselective preparation of l-7-bromotryptophan methyl ester 3 using a Corey-O'Donnell alkylation

  描述了作为潜在的蛋白酶体抑制剂的TMC-95A的三种受限大环肽类似物1的合成。关键步骤涉及Ni（0）介导的三肽2的大环化，该三肽2带有卤化芳族侧链，用于形成联芳基。另外，以良好的总收率和以非常高的ee（＞ 85％）在多克规模上获得了使用甘氨酸二苯甲酮亚胺的Corey-O'Donnell烷基化的1-7-溴色氨酸甲酯3的对映选择性制备。
• Linear TMC-95-Based Proteasome Inhibitors
  作者：Nicolas Basse、Sandrine Piguel、David Papapostolou、Alexandra Ferrier-Berthelot、Nicolas Richy、Maurice Pagano、Pierre Sarthou、Joëlle Sobczak-Thépot、Michèle Reboud-Ravaux、Joëlle Vidal

  DOI：10.1021/jm0701324

  日期：2007.6.1

  We have designed and evaluated 45 linear analogues of the natural constrained cyclopeptide TMC-95A. These synthetically less demanding molecules are based on the tripeptide sequence Y-N-W of TMC-95A. Structural variations in the amino acid side chains and termini greatly influenced both the efficiency and selectivity of action on a given type of active site. Inhibition constants were submicromolar (K-i approximate to 300 nM) despite the absence of the entropically favorable constrained conformation that is characteristic of TMC-95A and its cyclic analogues. These linear compounds were readily prepared and reasonably stable in culture medium and could be optimized to inhibit one, two, or all three proteasome catalytic sites. Cytotoxicity assays performed on a series of human tumor cell lines identified the most potent inhibitors in cells.