tert-butyl (9-benzyl-6-chloro-9H-purin-2-yl)carbamate | 1175562-20-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: tert-butyl (9-benzyl-6-chloro-9H-purin-2-yl)carbamate
• 英文别名: 9-benzyl-2-tert-butoxycarbonylamino-6-chloropurine；N2-Boc-9-benzyl-6-chloro-9H-purin-2-ylamine；tert-butyl N-(9-benzyl-6-chloropurin-2-yl)carbamate
• CAS: 1175562-20-5
• 化学式: C₁₇H₁₈ClN₅O₂
• 分子量: 359.815
• InChiKey: PNLWTWRRHWMSGP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  81.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (9-benzyl-6-chloro-9H-purin-2-yl)carbamate 在 ammonium hydroxide 、 copper(l) iodide 、 trans-bis(triphenylphosphine)palladium dichloride 、 三丁基膦 、 pyridinium hydrobromide perbromide 、 三氟乙酸 、 1,1'-azodicarbonyl-dipiperidine 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 24.0h， 生成
  参考文献：
  名称：

  8-Triazolylpurines: Towards Fluorescent Inhibitors of the MDM2/p53 Interaction

  摘要：

  小分子非肽类α-螺旋模拟物被广泛认可为蛋白质-蛋白质相互作用（PPIs）的抑制剂。蛋白质-蛋白质相互作用几乎介导了细胞内所有重要的调控通路，因此控制和调节PPIs的能力对基础生物学具有重大意义，其中对蛋白质网络的可控破坏是理解网络连接和功能的关键。我们设计和合成了两系列2,6,9-取代的8-三唑基嘌呤作为α-螺旋模拟物。第一系列基于低能构象设计，但在针对MDM2/p53的生物化学荧光偏振分析中未显示出任何生物活性。尽管溶液NMR构象研究表明这些分子可以模拟α-螺旋的拓扑结构，但对接研究表明这些化合物作为MDM2/p53相互作用的抑制剂并不最优。基于对接研究和最近发表的抑制剂分析，设计了新的8-三唑基嘌呤系列。最佳化合物在生物化学荧光偏振分析中显示出对MDM2/p53的低微摩尔抑制活性。为了评估这些化合物作为具有内在荧光活性的探针的适用性，测量了它们的吸收/发射特性。这些化合物显示出高达50%的量子产率的荧光特性。

  DOI：

  10.1371/journal.pone.0124423
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 4-二甲氨基吡啶 、 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 1.0h， 生成 tert-butyl (9-benzyl-6-chloro-9H-purin-2-yl)carbamate
  参考文献：
  名称：

  走向更多类似药物的蛋白质模拟物：基于嘌呤支架的两面合成α-螺旋模拟物†

  摘要：

  模仿α-螺旋的两个面可能会产生更有效和更具选择性的异常螺旋介导的蛋白质-蛋白质相互作用（PPI）抑制剂。在本文中，我们证明了2,6,9-三取代嘌呤能够通过有效模仿Bak-BH3α-螺旋相对面上的关键残基来破坏Mcl-1-Bak-BH3 PPI。

  DOI：

  10.1039/c5ob00478k

文献信息

• Facile and efficient access to 2,6,9-tri-substituted purines through sequential N9, N2 Mitsunobu reactions
  作者：Steven Fletcher、Vijay M. Shahani、Patrick T. Gunning

  DOI：10.1016/j.tetlet.2009.04.137

  日期：2009.7

  both Mitsunobu reactions. Significantly, excellent chemoselectivity and N9-regioselectivity were observed for the first coupling, and reactions were complete within 15 min at room temperature. Our novel methodology may be readily adapted to furnish N9-mono- or N2,N9-di-functionalized guanine analogues, and the utility of our protocol is further demonstrated by the efficient synthesis of the CDK inhibitor

  提出了一种2,6,9-三取代嘌呤的简便，有效和温和的合成方法，从市售的2-氨基-6-氯嘌呤开始，其采用先后顺序的N9然后N2 Mitsunobu反应作为关键步骤。重要的是，我们对嘌呤核进行N2官能化的合成方法消除了用伯胺将2-卤基团进行传统亲核芳香取代所需要的苛刻条件。在两次光延反应中，苯甲酸，烯丙基，炔丙基和脂肪族醇的收率都非常好。显着地，对于第一次偶联观察到优异的化学选择性和N9-区域选择性，并且在室温下15分钟内反应完成。我们新颖的方法很容易适应提供N 9-单-或N2，N 9-二官能化的鸟嘌呤类似物，并且我们的方案的实用性通过CDK抑制剂波西米因的有效合成得到进一步证明。
• Concise access to N9-mono-, N2-mono- and N2,N9-di-substituted guanines via efficient Mitsunobu reactions
  作者：Steven Fletcher、Vijay M. Shahani、Alan J. Lough、Patrick T. Gunning

  DOI：10.1016/j.tet.2010.03.118

  日期：2010.6

  Guanine poses several problems to the synthetic chemist owing to its polyfunctional nature and poor solubility. Over the past few decades, synthetic guanines have found applications as anti-cancer and anti-viral agents. Coupled with the ever-growing interest in designer PNAs and G-quartets, simple and efficient synthetic routes to novel guanines would be of significant benefit. We herein report that, upon simple protection and/or activation step(s), the guanine precursor 2-amino-6-chloropurine is rendered an excellent substrate for Mitsunobu chemistry, furnishing, after subsequent hydrolytic dechlorination and appropriate deprotection step(s), the desired N9-mono-, N2-mono- or N2,N9-di-substituted guanines in excellent yields (>= 80%). Importantly, we demonstrate that N9-functionalization proceeds with very good N9/N7 regioselectivity and with complete inversion of stereochemistry. (C) 2010 Elsevier Ltd. All rights reserved.
• 8-Bromination of 2,6,9-trisubstituted purines with pyridinium tribromide
  作者：David Bliman、Mariell Pettersson、Mattias Bood、Morten Grøtli

  DOI：10.1016/j.tetlet.2014.03.084

  日期：2014.4

  2,6,9-Trisubstituted purines are brominated in high yields using pyridinium tribromide as the brominating reagent. This procedure works excellently for electron-rich purines having electron-donating substituents at the 2- and 6-positions. The use of pyridinium tribromide, a crystalline alternative to elemental bromine, improves the bromination procedure for this type of substrate as the reagent is easy to handle and the work-up and purification procedures are simplified. (C) 2014 The Authors. Published by Elsevier Ltd.
• Towards more drug-like proteomimetics: two-faced, synthetic α-helix mimetics based on a purine scaffold
  作者：M. E. Lanning、P. T. Wilder、H. Bailey、B. Drennen、M. Cavalier、L. Chen、J. L. Yap、M. Raje、S. Fletcher

  DOI：10.1039/c5ob00478k

  日期：——

  Mimicry of two faces of an α-helix might yield more potent and more selective inhibitors of aberrant, helix-mediated protein–protein interactions (PPI). Herein, we demonstrate that a 2,6,9-tri-substituted purine is capable of disrupting the Mcl-1-Bak-BH3 PPI through effective mimicry of key residues on opposing faces of the Bak-BH3 α-helix.

  模仿α-螺旋的两个面可能会产生更有效和更具选择性的异常螺旋介导的蛋白质-蛋白质相互作用（PPI）抑制剂。在本文中，我们证明了2,6,9-三取代嘌呤能够通过有效模仿Bak-BH3α-螺旋相对面上的关键残基来破坏Mcl-1-Bak-BH3 PPI。
• 8-Triazolylpurines: Towards Fluorescent Inhibitors of the MDM2/p53 Interaction
  作者：Mariell Pettersson、David Bliman、Jimmy Jacobsson、Jesper R. Nilsson、Jaeki Min、Luigi Iconaru、R. Kiplin Guy、Richard W. Kriwacki、Joakim Andréasson、Morten Grøtli

  DOI：10.1371/journal.pone.0124423

  日期：——

  Small molecule nonpeptidic mimics of α-helices are widely recognised as protein-protein interaction (PPIs) inhibitors. Protein-protein interactions mediate virtually all important regulatory pathways in a cell, and the ability to control and modulate PPIs is therefore of great significance to basic biology, where controlled disruption of protein networks is key to understanding network connectivity and function. We have designed and synthesised two series of 2,6,9-substituted 8-triazolylpurines as α-helix mimetics. The first series was designed based on low energy conformations but did not display any biological activity in a biochemical fluorescence polarisation assay targeting MDM2/p53. Although solution NMR conformation studies demonstrated that such molecules could mimic the topography of an α-helix, docking studies indicated that the same compounds were not optimal as inhibitors for the MDM2/p53 interaction. A new series of 8-triazolylpurines was designed based on a combination of docking studies and analysis of recently published inhibitors. The best compound displayed low micromolar inhibitory activity towards MDM2/p53 in a biochemical fluorescence polarisation assay. In order to evaluate the applicability of these compounds as biologically active and intrinsically fluorescent probes, their absorption/emission properties were measured. The compounds display fluorescent properties with quantum yields up to 50%.

  小分子非肽类α-螺旋模拟物被广泛认可为蛋白质-蛋白质相互作用（PPIs）的抑制剂。蛋白质-蛋白质相互作用几乎介导了细胞内所有重要的调控通路，因此控制和调节PPIs的能力对基础生物学具有重大意义，其中对蛋白质网络的可控破坏是理解网络连接和功能的关键。我们设计和合成了两系列2,6,9-取代的8-三唑基嘌呤作为α-螺旋模拟物。第一系列基于低能构象设计，但在针对MDM2/p53的生物化学荧光偏振分析中未显示出任何生物活性。尽管溶液NMR构象研究表明这些分子可以模拟α-螺旋的拓扑结构，但对接研究表明这些化合物作为MDM2/p53相互作用的抑制剂并不最优。基于对接研究和最近发表的抑制剂分析，设计了新的8-三唑基嘌呤系列。最佳化合物在生物化学荧光偏振分析中显示出对MDM2/p53的低微摩尔抑制活性。为了评估这些化合物作为具有内在荧光活性的探针的适用性，测量了它们的吸收/发射特性。这些化合物显示出高达50%的量子产率的荧光特性。