1,4-bis<3-(5-nitro-6-D-ribitylaminouracilyl)>butane | 228396-48-3

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: 1,4-bis<3-(5-nitro-6-D-ribitylaminouracilyl)>butane
• 英文别名: 5-nitro-3-[4-[5-nitro-2,4-dioxo-6-[[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]amino]-1H-pyrimidin-3-yl]butyl]-6-[[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]amino]-1H-pyrimidine-2,4-dione
• CAS: 228396-48-3
• 化学式: C₂₂H₃₄N₈O₁₆
• 分子量: 666.556
• InChiKey: SBODWXGGWSCQAS-GKBVHCHNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.6
• 重原子数：
  46
• 可旋转键数：
  17
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  376
• 氢给体数：
  12
• 氢受体数：
  18

反应信息

• 作为反应物：
  描述：

  1,4-bis<3-(5-nitro-6-D-ribitylaminouracilyl)>butane 在 10percent Pd/C 氢气 作用下， 以 水 为溶剂， 反应 12.0h， 生成 5-amino-3-[4-[5-amino-2,4-dioxo-6-[[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]amino]-1H-pyrimidin-3-yl]butyl]-6-[[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]amino]-1H-pyrimidine-2,4-dione
  参考文献：
  名称：

  设计，合成和评估9-D-ribityl-1,3,7-三氢-2,6,8-嘌呤三酮（一种核黄素合酶和lumazine合酶的有效抑制剂）。

  摘要：

  还原5-硝基-6-D-核糖基氨基尿嘧啶（9），得到5-氨基-6-D-核糖基氨基尿嘧啶（1），其与氯甲酸乙酯反应生成5-乙基氨基甲酰基-6-D-核糖基氨基尿嘧啶（12）。将后者化合物环化成9-D-ribityl-1,3,7-三氢嘌呤-2,6,8-三酮（13），发现它是两种大肠杆菌核黄素合酶（K（i ）0.61 microM）和枯草芽孢杆菌lumazine合酶（K（i）46 microM）。LUM嗪合酶-抑制剂复合物的分子模型表明该酶的Lys135ε-氨基与配体的8-酮基和4'-羟基均存在氢键结合的可能性。核黄素合酶催化反应的双底物类似物1,4-双[1-（9-D-ribityl-1,3,7-三氢嘌呤-2,6,8-三酰基）]丁烷（18），

  DOI：

  10.1021/jo010706r
• 作为产物：
  描述：

  1,4-bis<3-(1-methoxymethyl-6-chlorouracilyl)>butane 在 硫酸 、 硝酸 作用下， 以 乙醇 、 水 为溶剂， 反应 16.5h， 生成 1,4-bis<3-(5-nitro-6-D-ribitylaminouracilyl)>butane
  参考文献：
  名称：

  Synthesis and Biochemical Evaluation of Bis(6,7-dimethyl-8-d-ribityllumazines) as Potential Bisubstrate Analogue Inhibitors of Riboflavin Synthase

  摘要：

  The reaction catalyzed by riboflavin synthase utilizes two identical 6,7-dimethyl-8-n-ribityllumazine substrate molecules. Three bis(6,7-dimethyl-8-D-ribityllumazines) were, therefore, synthesized in which the two lumazine moieties were connected through their N-3 nitrogen atoms by polymethylene linker chains containing three, four, and five carbon atoms. The compounds with three and five carbon linkers were found to be very weak inhibitors of riboflavin synthase, having inhibition constants of 320 and >1000 mu M, respectively. In contrast, the bis(lumazine) with a four-carbon linker was much more potent, with an inhibition constant of 37 mu M. These results have potential implications for understanding the distance between the donor and acceptor sites of riboflavin synthase and the orientations of the two 6,7-dimethyl-8-D-ribityllumazine substrate molecules which occupy these two sites.

  DOI：

  10.1021/jo9821731

文献信息

• Design, Synthesis, and Evaluation of 9-<scp>d</scp>-Ribityl-1,3,7-trihydro-2,6,8-purinetrione, a Potent Inhibitor of Riboflavin Synthase and Lumazine Synthase
  作者：Mark Cushman、Donglai Yang、Klaus Kis、Adelbert Bacher

  DOI：10.1021/jo010706r

  日期：2001.12.1

  compound was cyclized to 9-D-ribityl-1,3,7-trihydropurine-2,6,8-trione (13), which was found to be a relatively potent inhibitor of both Escherichia coli riboflavin synthase (K(i) 0.61 microM) and Bacillus subtilis lumazine synthase (K(i) 46 microM). Molecular modeling of the lumazine synthase-inhibitor complex indicated the possibility for hydrogen bonding between the Lys135 epsilon-amino group of the

  还原5-硝基-6-D-核糖基氨基尿嘧啶（9），得到5-氨基-6-D-核糖基氨基尿嘧啶（1），其与氯甲酸乙酯反应生成5-乙基氨基甲酰基-6-D-核糖基氨基尿嘧啶（12）。将后者化合物环化成9-D-ribityl-1,3,7-三氢嘌呤-2,6,8-三酮（13），发现它是两种大肠杆菌核黄素合酶（K（i ）0.61 microM）和枯草芽孢杆菌lumazine合酶（K（i）46 microM）。LUM嗪合酶-抑制剂复合物的分子模型表明该酶的Lys135ε-氨基与配体的8-酮基和4'-羟基均存在氢键结合的可能性。核黄素合酶催化反应的双底物类似物1,4-双[1-（9-D-ribityl-1,3,7-三氢嘌呤-2,6,8-三酰基）]丁烷（18），
• Synthesis and Biochemical Evaluation of Bis(6,7-dimethyl-8-<scp>d</scp>-ribityllumazines) as Potential Bisubstrate Analogue Inhibitors of Riboflavin Synthase
  作者：Mark Cushman、Farahnaz Mavandadi、Donglai Yang、Karl Kugelbrey、Klaus Kis、Adelbert Bacher

  DOI：10.1021/jo9821731

  日期：1999.6.1

  The reaction catalyzed by riboflavin synthase utilizes two identical 6,7-dimethyl-8-n-ribityllumazine substrate molecules. Three bis(6,7-dimethyl-8-D-ribityllumazines) were, therefore, synthesized in which the two lumazine moieties were connected through their N-3 nitrogen atoms by polymethylene linker chains containing three, four, and five carbon atoms. The compounds with three and five carbon linkers were found to be very weak inhibitors of riboflavin synthase, having inhibition constants of 320 and >1000 mu M, respectively. In contrast, the bis(lumazine) with a four-carbon linker was much more potent, with an inhibition constant of 37 mu M. These results have potential implications for understanding the distance between the donor and acceptor sites of riboflavin synthase and the orientations of the two 6,7-dimethyl-8-D-ribityllumazine substrate molecules which occupy these two sites.