2'-脱氧-8-(9H-芴-2-基氨基)-鸟苷 | 73051-69-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 中文名称: 2'-脱氧-8-(9H-芴-2-基氨基)-鸟苷
• 中文别名: 3-苯氧基丙酰氯化；2′-脱氧-8-(9H-芴-2-基氨基)-鸟苷
• 英文名称: N-(2'-deoxyguanosin-8-yl)-2-aminofluorene
• 英文别名: N-(Deoxyguanosin-8-yl)-2-aminofluorene；2-amino-8-(9H-fluoren-2-ylamino)-9-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1H-purin-6-one
• CAS: 73051-69-1
• 化学式: C₂₃H₂₂N₆O₄
• 分子量: 446.465
• InChiKey: RMYQNJYFBAYPNG-RCCFBDPRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  33
• 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：
  147
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2'-脱氧-8-(9H-芴-2-基氨基)-鸟苷 在 aqueous buffer 作用下， 生成 N-(9H-Fluoren-2-yl)-N'-((2R,4S,5R)-4-hydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-guanidine
  参考文献：
  名称：

  Facile aerial oxidation of the DNA-base adduct N-(2'-deoxyguanosin-8-yl)-2-aminofluorene [dG(C8)AF]

  摘要：

  DOI：

  10.1021/ja00170a056
• 作为产物：
  描述：

  N-羟基-2-氨基芴 在 甲醇 、 sodium carbonate 作用下， 以 乙醇 、 苯 为溶剂， 反应 20.17h， 生成 2'-脱氧-8-(9H-芴-2-基氨基)-鸟苷
  参考文献：
  名称：

  α-苯基-N-(2-氨基芴基)硝酮和N-(2'-Deoxyguanosin-8-yl)-2-氨基芴的LTA氧化合成终极致癌物N-乙酰氧基-N-苯甲酰基-2-氨基芴

  摘要：

  在四乙酸铅 (LTA) 氧化中实现了新的 α-苯基-N-(2-氨基芴基)硝酮 (8) 重排为新的终极致癌物 N-乙酰氧基-N-苯甲酰基-2-氨基芴 (9)反应。化合物 9 在 pH 7.0 下与脱氧鸟苷 (dG) 反应生成 N-(苯甲酰基)-N-(脱氧鸟苷-8-基)-2-氨基芴 (10)。随后用非均相系统（碳酸钠/甲醇）进行脱苯甲酰化，生成 C8 加合物 N-(2'-deoxyguanosin-8-yl)-2-aminofluorene (11)。

  DOI：

  10.1055/s-2001-18718

文献信息

• Synthesis of DNA Strands Site-Specifically Damaged by C8-Arylamine Purine Adducts and Effects on Various DNA Polymerases
  作者：Nicolas Böge、Maike I. Jacobsen、Zita Szombati、Sabrina Baerns、Francesca Di Pasquale、Andreas Marx、Chris Meier

  DOI：10.1002/chem.200800979

  日期：2008.12.8

  C8-Arylamine-dG and C8-arylamine-dA adducts have been prepared using palladium cross-coupling chemistry. These adducts were subsequently converted into the corresponding 5'-O-DMTr-C8-arylamine-3'-O-phosphoramidites and then used for the automated synthesis of different site-specifically modified oligonucleotides. These "damaged" oligonucleotides have been characterized by ESI-MS, UV thermal stability

  使用钯交叉偶联化学已经制备了C8-芳胺-dG和C8-芳基胺-dA加合物。随后将这些加合物转化为相应的5'-O-DMTr-C8-芳基胺-3'-O-亚磷酰胺，然后用于自动合成不同的位点特异性修饰的寡核苷酸。这些“损坏”的寡核苷酸已通过ESI-MS，UV热稳定性测定和圆二色性进行了表征，它们已用于EcoRI测定以及使用各种DNA聚合酶的引物延伸研究中。
• Reaction of arylnitrenium ions with guanine derivatives: <i>N</i>¹-methylguanosine and <i>N</i>²,<i>N</i>²-dimethylguanosine
  作者：Bernice Cheng、Robert A McClelland

  DOI：10.1139/v01-179

  日期：2001.12.1

  A prior flash photolysis study of the direct reaction of arylnitrenium ions with 2'-deoxyguanosine identified a second intermediate that grew in as the transient nitrenium ion reacted with the nucleoside. This intermediate was identified as the the product of the addition of the nitrenium ion to the C-8 position of guanine prior to loss of the C-8 proton — the C-8 intermediate. A feature of the C-8 intermediate is that it exists in acid–base forms. This behavior was evident in both a spectroscopic analysis as well as in the rate–pH profile, which showed a break around pH 4 from a pH-independent reaction to a reaction that was first-order in H⁺. The present study was designed to identify the structure of the conjugate base form. This involved a kinetic study of the decay of the C-8 intermediate derived from the reaction of the 2-fluorenylnitrenium ion with N¹-methylguanosine and N²,N²-dimethylguanosine. The rationale was that the former is unable to lose the N-1 proton, while the latter cannot deprotonate at the NH₂ group. The rate–pH profiles clearly show that it is the N-1 proton that is acidic. The rate constants for the C-8 intermediate of N²,N²-dimethylguanosine show the same downward break observed with 2'-deoxyguanosine and guanosine associated with conversion to the conjugate base form. In contrast, the rate constants for the N¹-methylguanosine intermediate are independent of pH. Rate constants for the reaction forming the C-8 intermediate are also reported. These show that the reaction of nitrenium ions with the N²,N²-dimethylguanine derivative is significantly faster (except where the reactions are diffusion controlled). This is consistent with the initial step of the reaction of an arylnitrenium ion and guanine occurring by direct addition at C-8. The developing positive charge in such a reaction can be delocalized to the C-2 position where π donors such as NH₂ and NMe₂ can exert a stabilizing effect.Key words: nitrenium, arylnitrenium, guanosine, DNA adduct.

  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。
• Site-Specific Synthesis and Properties of Oligonucleotides Containing C8-Deoxyguanosine Adducts of the Dietary Mutagen IQ
  作者：C. Eric Elmquist、James S. Stover、Zhiwei Wang、Carmelo J. Rizzo

  DOI：10.1021/ja0487022

  日期：2004.9.1

  The site-specific synthesis of oligonucleotides containing the C8-deoxyguanosine adduct of the highly mutagenic heterocyclic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) has been achieved, and the oligonucleotides were characterized by UV melting temperature analysis, circular dichroism, and UV absorption spectroscopy. Examination of these data indicated that the IQ-adduct is accommodated in

  已实现含有高致突变杂环胺2-氨基-3-甲基咪唑并[4,5-f]喹啉(IQ)的C8-脱氧鸟苷加合物的寡核苷酸的定点合成，并通过UV熔解温度表征寡核苷酸分析、圆二色性和紫外吸收光谱。对这些数据的检查表明 IQ 加合物适应于截然不同的环境。这种依赖于序列的构象偏好可能在 IQ 修饰的寡核苷酸的致突变性和修复中发挥关键作用。
• A practical approach for the chemical synthesis of 2′-deoxyguanosine-C8 adducts with mutagenic/carcinogenic amino- or nitro-arenes
  作者：Takeji Takamura-Enya、Satoko Ishikawa、Masataka Mochizuki、Keiji Wakabayashi

  DOI：10.1016/s0040-4039(03)01484-9

  日期：2003.8

  of 2′-deoxyguanosine-C8 (dG-C8) adducts with several mutagenic and carcinogenic amino- or nitro-arenes were developed using the palladium-mediated cross-coupling reaction of protected 8-amino-dG with bromoarenes in around 80% yields, followed by conventional deprotection procedures. This approach can be applied to preparation of a variety of authentic dG-C8 adducts with amino or nitro-arenes.

  利用钯介导的受保护的8-氨基-dG与溴代芳烃的交叉偶联反应，开发了合成具有几种致突变和致癌的氨基或硝基芳烃的2'-脱氧鸟苷-C8（dG-C8）加合物的合成方法。大约80％的收率，然后进行常规的脱保护程序。该方法可用于制备各种带有氨基或硝基芳烃的可靠的dG-C8加合物。
• Substituent effects on the bioactivation of 2-(N-hydroxyacetamido)fluorenes by N-arylhydroxamic acid N,O-acyltransferase
  作者：Adnan A. Elfarra、Patrick E. Hanna

  DOI：10.1021/jm00148a014

  日期：1985.10

  A series of 7-substituted analogues of 2-(N-hydroxyacetamido)fluorene (1) was subjected to bioactivation by a partially purified preparation of hamster hepatic AHAT, and the rates of methylthio adduct formation resulting from the reaction of the activated intermediates with N-acetylmethionine were determined. Electronegative substituents enhanced the amount of adduct formed; this finding contrasted

  通过部分纯化的仓鼠肝AHAT制备一系列2-（N-羟基乙酰氨基）芴（1）的7-取代类似物，进行生物活化，以及由活化的中间体与N反应生成的甲硫基加合物的形成速率测定了乙酰乙酰蛋氨酸。负电子取代基增加了加合物的形成；这一发现与先前的研究结果相反，在先前的研究中，给电子取代基通过1的类似物促进了AHAT的基于机理的失活。加合物的结构是由7种化合物中几种活化形式的反应形成的测定了用N-乙酰甲硫氨酸和2'-脱氧鸟苷取代的化合物；