N-(2'-deoxypyranosin-8-yl)-4-methylaniline | 126788-73-6

• 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: N-(2'-deoxypyranosin-8-yl)-4-methylaniline
• 英文别名: 8-(4-methylphenylamino)-2'-deoxyguanosine；N-(2'-deoxyguanosin-8-yl)-4-methylaniline；N-(Desoxyguanosin-8-yl)-4-methylaniline；N-(Desoxyguanosin-8-yl)-4-methylanilin；2-amino-9-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-8-(4-methylanilino)-1H-purin-6-one
• CAS: 126788-73-6
• 化学式: C₁₇H₂₀N₆O₄
• 分子量: 372.384
• InChiKey: SHOPSBOWUOUXGM-QJPTWQEYSA-N

物化性质

• 密度：
  1.72±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 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：

  N-(2'-deoxypyranosin-8-yl)-4-methylaniline 、 N,N-二甲基甲酰胺二乙基缩醛 在 吡啶 作用下， 反应 16.0h， 生成
  参考文献：
  名称：

  Synthesis of DNA-Oligonucleotides Damaged by Arylamine-Modified 2′-Deoxyguanosine

  摘要：

  C8-Arylamine-dG adducts bearing a labile N-formamidine group at the exocyclic amino function were converted into their corresponding 5'-O-DMTr-3'-0-phosphoramidite-C8-arylamine-dG derivatives. These compounds were used for the automated synthesis of site-specifically modified oligonucleotides. These oligonucleotides were characterized by ESI-MS and enzymatic digestion and studied for their CD properties and T-m values.

  DOI：

  10.1080/15257770701490738
• 作为产物：
  描述：

  N-(对甲苯基)羟胺 在 sodium citrate buffer 、 sodium carbonate 作用下， 以 甲醇 、 乙醇 、 苯 为溶剂， 反应 16.25h， 生成 N-(2'-deoxypyranosin-8-yl)-4-methylaniline
  参考文献：
  名称：

  芳基硝酮的四乙酸铅氧化衍生的模型终极致癌物/代谢物的合成和表征：2'-脱氧鸟苷加合物

  摘要：

  描述了通过芳基硝酮 3a-c 的四乙酸铅 (LTA) 氧化合成模型反应性代谢物 4a-c。化合物 4a-c 与脱氧鸟苷 (dG) 反应生成 N-苯甲酰化 C8-加合物 5a-c。用非均相系统（碳酸钠/甲醇）脱苯甲酰后，得到相应的 C8 加合物 6a-c。

  DOI：

  10.1055/s-2001-16096

文献信息

• Synthesis, Characterization, and Conformational Analysis of DNA Adducts from Methylated Anilines Present in Tobacco Smoke
  作者：M. Matilde Marques、Luísa L. G. Mourato、M. Amélia Santos、Frederick A. Beland

  DOI：10.1021/tx950044z

  日期：1996.1.1

  to the arylamine nitrogen had a higher percentage of syn conformers. This observation was supported by theoretical simulation studies that indicated substantial percentages of low energy syn conformers, increasing with the substitution pattern in the order para < meta < ortho < ortho,para < ortho,meta. The results demonstrate that, although single-ring arylamines are considered weak carcinogens, their

  烟草烟雾中存在的一系列芳香胺（2-，3-和4-甲基苯胺，2,3-和2,4-二甲基苯胺）与DNA结合的能力已通过N-（酰氧基）芳基胺的反应进行了研究带有dG，dG核苷酸和DNA。通过光谱法和HPLC法将与dG和核苷酸反应的主要产物表征为N-（脱氧鸟苷-8-基）芳基胺。修饰DNA的HPLC和光谱分析表明相同的加合物。1 H和13 C NMR光谱的分析表明，含有在芳基胺氮上邻位的甲基取代基的加合物具有较高百分比的顺式构象异构体。这一观察结果得到理论模拟研究的支持，该研究表明低能同构异构体的百分比很高，并且随着取代模式的增加，其对位
• 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。
• 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。
• New Syntheses of DNA Adducts from Methylated Anilines Present in Tobacco Smoke
  作者：Paula S. Branco、Alexandra M. M. Antunes、M. Matilde Marques、M. Paul Chiarelli、Ana M. Lobo、Sundaresan Prabhakar

  DOI：10.1021/tx9901229

  日期：1999.12.1

  A new synthetic pathway for the formation of deoxyguanosine-monoarylamine adducts is described, involving the generation and use of arylnitrenes as electrophilic synthons. Photolysis of aryl azides, the most common method for generating arylnitrenes, was tested in the presence of 2'-deoxyguanosine. N-(2'-Deoxyguanosin-8-yl)monoarylamine (dG-C8-Ar) adducts were obtained, but the yields were typically

  描述了形成脱氧鸟苷-单芳基胺加合物的新合成途径，涉及芳基硝烯作为亲电合成子的产生和使用。在2'-脱氧鸟苷的存在下测试了芳基叠氮化物的光解反应，这是最常见的芳基氮化物生成方法。获得了N-（2'-脱氧鸟苷-8-基）单芳基胺（dG-C8-Ar）加合物，但收率通常较低。亚磷酸三乙酯在2'-脱氧鸟嘌呤存在下用亚磷酸三乙酯对亚硝基和亚硝基芳烃进行脱氧是一种有效的方法，通过该方法，dG-C8-Ar，（2'-脱氧鸟苷-N1-基）单芳基胺（dG-N1-Ar） ，和（2'-deoxyguanosin-O（6）-yl）monoarylamine（dG-O（6）-Ar）加合物以可接受的产率获得。
• Synthesis and Quantification of DNA Adducts of 4,4‘-Methylenedianiline
  作者：Dietrich Schütze、Peter Sagelsdorff、Ovnair Sepai、Gabriele Sabbioni

  DOI：10.1021/tx950194+

  日期：1996.1.1

  4,4'-Methylenedianiline (MDA) is used as a hardener in the manufacture of plastics and polyurethanes. MDA has been classified as a carcinogen in animals and is a suspected human carcinogen. Assuming that MDA would yield similar DNA adducts to other arylamines, we synthesized the following C-8 guanine adducts: N'-acetyl-N-(deoxyguanosin-8-yl)-MDA, N-(deoxyguanosin-8-yl)-MDA, N-(deoxyguanosin-8-yl)-4MA, and their corresponding 3'-monophosphate derivatives. We developed methods to identify these adducts of MDA in liver DNA using P-32-postlabeling, HPLC, and GC-MS techniques. Liver DNA was obtained from rats treated with radiolabeled MDA (1.11 and 116.5 mu mol/kg body weight). The total radioactivity bound to the DNA corresponded to 0.06 and 2.7 adducts per 10(7) nucleotides [covalent binding index (CBI=(mu mol of adduct per mol of nucleotide)/(mmol of compound per kg body weight)) of 1.05 and 2.3]. This DNA-binding potency is in the range of weakly genotoxic compounds. The liver DNA was analyzed for the presence of the synthesized adducts by the following methods: (I) HPLC analysis of nucleotides and purines after enzymatic and acid hydrolysis, and (II) P-32-postlabeling after enzymatic hydrolysis. The major adducts found in vivo did not correspond to the synthesized standards. Further work was carried out to determine the structure of the unidentified adducts. It was possible to release MDA and MDA-d(4) from DNA of rats dosed with MDA and/or MDA-d(4) and from the synthesized adducts using strong base hydrolysis. Liver of two female Wistar rats given 500 mu mol/kg MDA . 2HCl was hydrolyzed in 0.1 M NaOH overnight at 110 degrees C. GC-MS analysis of the heptafluorobutyric anhydride derivatized dichloromethane extracts detected 428+/-40 fmol of MDA/mg of DNA. In the control animals no MDA was found. The experiment was repeated with livers from animals dosed 500 mu mol/kg MDA-d(4) . 2HCl. In these rats 488+/-19 fmol MDA-d(4) was found to be bound at liver DNA. Taking into account a 68% yield of the method, the CBI found in these cases was 0.82 and 1.0, respectively.