C⁸-(2-aminofluorenyl)Guo | 16699-28-8

• 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: C⁸-(2-aminofluorenyl)Guo
• 英文别名: 2-Amino-8-(fluoren-2-ylamino)inosine；2-amino-9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-8-(9H-fluoren-2-ylamino)-1H-purin-6-one
• CAS: 16699-28-8
• 化学式: C₂₃H₂₂N₆O₅
• 分子量: 462.465
• InChiKey: JIZHFPQGDVSPBL-QTQZEZTPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  34
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  167
• 氢给体数：
  6
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-Amino-9-((2R,3R,4S,5R)-3,4-dihydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-8-(9H-fluoren-2-ylamino)-6-oxo-6,8-dihydro-1H-purin-9-ium 在 水 作用下， 生成 C⁸-(2-aminofluorenyl)Guo
  参考文献：
  名称：

  Reaction of arylnitrenium ions with guanine derivatives: N¹-methylguanosine and N²,N²-dimethylguanosine

  摘要：

  一项先前的闪光光解研究表明，芳基亚硝基离子与2'-脱氧鸟苷直接反应时产生了第二个中间体，随着瞬态亚硝基离子与核苷反应，这个中间体逐渐增加。这个中间体被确定为亚硝基离子加成到鸟嘌呤的C-8位置形成的产物，在失去C-8质子之前形成的C-8中间体。C-8中间体的一个特征是它存在酸碱形式。这种行为在光谱分析和速率-pH曲线中都很明显，速率-pH曲线显示在pH 4左右出现了从pH无关反应到首级H⁺反应的转变。本研究旨在确定共轭碱形式的结构。这涉及对由2-芴亚硝基离子与N¹-甲基鸟嘌呤和N²,N²-二甲基鸟嘌呤反应产生的C-8中间体衰减的动力学研究。其理论基础是前者无法失去N-1质子，而后者无法在NH₂基团上去质子。速率-pH曲线清楚地显示N-1质子是酸性的。N²,N²-二甲基鸟嘌呤的C-8中间体的速率常数显示与2'-脱氧鸟嘌呤和鸟嘌呤相关的向共轭碱形式转变的下降变化。相比之下，N¹-甲基鸟嘌呤中间体的速率常数与pH无关。还报告了形成C-8中间体的反应速率常数。这些结果表明，芳基亚硝基离子与N²,N²-二甲基鸟嘌呤衍生物的反应速度明显更快（除非反应受扩散控制）。这与芳基亚硝基离子和鸟嘌呤的反应的初始步骤发生在C-8位置的直接加成一致。在这种反应中产生的正电荷可以共轭到C-2位置，π给体如NH₂和NMe₂可以发挥稳定作用。关键词：亚硝基、芳基亚硝基、鸟苷、DNA加合物。

  DOI：

  10.1139/v01-179

文献信息

• Formation and Reactions of <i>N</i>⁷-Aminoguanosine and Derivatives
  作者：F. Peter Guengerich、Ralf G. Mundkowski、Markus Voehler、Fred F. Kadlubar

  DOI：10.1021/tx990094u

  日期：1999.10.1

  Arylamines are mutagens and carcinogens and are thought to initiate tumors by forming adducts with DNA. The major adducts are C-8-guanyl, and we have previously suggested a role for guanyl-N-7 intermediates in the formation process. N-7-Aminoguanosine (Guo) was synthesized and characterized, with the position of the NH2 at N7 established by two-dimensional rotating frame Overhauser enhancement NMR spectroscopy. In DMF, N-7-NH(2)Guo formed C-8-NH(2)Guo and the cyclic product C-8:5'-O-cycloGuo. In aqueous media, these products were formed along with 8-oxo-7,8-dihydroGuo, N-7-NH(2)guanine, and a product characterized as a purine 8,9-ring-opened derivative (N-aminoformamidopyrimidine). The rate of aqueous decomposition of N-7-NH(2)Guo increased with pH, with a t(1/2) of 10 h at pH 7 and a t(1/2) of 2 h at pH 9. The rate of migration of NH2 from N7 to C8 is fast enough to explain the formation of C-8-NH(2)Guo from the reaction of 2,4-dinitrophenoxyamine with Guo but not the formation of C-8-(arylamino)Guo in the reaction of Guo with aryl hydroxylamine esters; however, the fluorenyl moiety may facilitate the proposed rearrangement by stabilizing an incipient negative charge in the transfer. In the reaction of Guo with N-hydroxy-2-aminofluorene and acetylsalicylic acid, a peak with the mass spectrum expected for N-7-(2-aminofluorenyl)Guo was detected early in the reaction and was distinguished from C-8-(2-aminofluorenyl)Guo. NMR experiments with [8-C-13]Guo also provided some additional support for transient formation of N-7-(2-aminofluorenyl)Guo. We conclude that a guanyl-N-7 intermediate is reasonable in the reaction of activated arylamines with nucleic acids, although an exact rate of transfer of an N-7-arylamine group to the C8 position has not yet been quantified. The results provide an explanation for the numerous products associated with modification of DNA by activate arylamines. However, the contribution of "direct" reaction at the guanine C8 atom cannot be excluded.