((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl 2-(3-bromophenyl)acetate

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: ((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl 2-(3-bromophenyl)acetate
• 英文别名: [(3aR,4R,6R,6aR)-4-(6-aminopurin-9-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methyl 2-(3-bromophenyl)acetate
• 化学式: C₂₁H₂₂BrN₅O₅
• 分子量: 504.34
• InChiKey: DEJSZYYFJDOPLU-AEVYOOLXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  124
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  ((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl 2-(3-bromophenyl)acetate 在 三氟乙酸 作用下， 以 二氯甲烷 、 水 为溶剂， 以55.4%的产率得到((2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl 2-(3-bromophenyl)acetate
  参考文献：
  名称：

  Adenosine analogs as inhibitors of tyrosyl-tRNA synthetase: Design, synthesis and antibacterial evaluation

  摘要：

  Herein we describe the synthesis and evaluation of a series of adenosine analogs for in vitro antibacterial activity against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Out of these compounds, compound c6 has much stronger antibacterial potency against Pseudomonas aeruginosa than ciprofloxacin, and was determined to target tyrosyl-tRNA synthetase with IC50 zof 0.8 +/- 0.07 mu M. Structure-activity relationship analysis suggested that introduction of a fluorine atom at the 3'-position of benzene ring of the phenylacetyl moiety significantly increased affinities to the enzyme. In comparison with isopropylidene analogs, 2',3'-deprotected compounds displayed higher inhibitory activity. Molecular dockings provided an explanation for observations in biological assays. (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.09.018
• 作为产物：
  描述：

  3-溴苯乙酸 、 2',3'-异丙叉腺苷 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 以63.1%的产率得到((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl 2-(3-bromophenyl)acetate
  参考文献：
  名称：

  Adenosine analogs as inhibitors of tyrosyl-tRNA synthetase: Design, synthesis and antibacterial evaluation

  摘要：

  Herein we describe the synthesis and evaluation of a series of adenosine analogs for in vitro antibacterial activity against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Out of these compounds, compound c6 has much stronger antibacterial potency against Pseudomonas aeruginosa than ciprofloxacin, and was determined to target tyrosyl-tRNA synthetase with IC50 zof 0.8 +/- 0.07 mu M. Structure-activity relationship analysis suggested that introduction of a fluorine atom at the 3'-position of benzene ring of the phenylacetyl moiety significantly increased affinities to the enzyme. In comparison with isopropylidene analogs, 2',3'-deprotected compounds displayed higher inhibitory activity. Molecular dockings provided an explanation for observations in biological assays. (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.09.018

文献信息

• Adenosine analogs as inhibitors of tyrosyl-tRNA synthetase: Design, synthesis and antibacterial evaluation
  作者：Wei Wei、Wei-Kang Shi、Peng-Fei Wang、Xiao-Tong Zeng、Pan Li、Ji-Rong Zhang、Qian Li、Zhi-Ping Tang、Jia Peng、Lang-Zhou Wu、Mei-Qun Xie、Chan Liu、Xian-Hui Li、Ying-Chun Wang、Zhu-Ping Xiao、Hai-Liang Zhu

  DOI：10.1016/j.bmc.2015.09.018

  日期：2015.10

  Herein we describe the synthesis and evaluation of a series of adenosine analogs for in vitro antibacterial activity against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Out of these compounds, compound c6 has much stronger antibacterial potency against Pseudomonas aeruginosa than ciprofloxacin, and was determined to target tyrosyl-tRNA synthetase with IC50 zof 0.8 +/- 0.07 mu M. Structure-activity relationship analysis suggested that introduction of a fluorine atom at the 3'-position of benzene ring of the phenylacetyl moiety significantly increased affinities to the enzyme. In comparison with isopropylidene analogs, 2',3'-deprotected compounds displayed higher inhibitory activity. Molecular dockings provided an explanation for observations in biological assays. (c) 2015 Elsevier Ltd. All rights reserved.