8-(4-methylphenyl)-2'-deoxyguanosine

• 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: 8-(4-methylphenyl)-2'-deoxyguanosine
• 英文别名: 2-amino-9-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-8-(4-methylphenyl)-1H-purin-6-one
• 化学式: C₁₇H₁₉N₅O₄
• 分子量: 357.369
• InChiKey: PHGGFLCRWDMFNI-QJPTWQEYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  135
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  8-(4-methylphenyl)-2'-deoxyguanosine 在 盐酸 作用下， 以 水 为溶剂， 生成 2-Amino-8-p-tolyl-1,9-dihydro-purin-6-one
  参考文献：
  名称：

  关于8芳基-2'-脱氧鸟苷核苷加合物的水解稳定性：生理pH下无碱基位点形成的意义。

  摘要：

  将芳基自由基种直接加到2'-脱氧鸟苷（dG）的C 8位上可得到C 8-芳基-dG加合物，其由致癌的芳基肼，多环芳烃（PAH）和某些酚类毒素产生。C 8-芳基嘌呤加合的共同性质是无碱基位点形成的伴随。为了确定C 8-芳基部分如何导致糖损失，已使用紫外可见光谱法确定N 7 p K a1值和水解动力学，同时利用密度泛函理论（DFT）计算来探究结构特征和C 8的稳定性带有不同对和邻取代基的-芳基-dG加合物。在所有情况下，将C 8 -芳基-dG加合物采取顺含有强ø构象5 '-H···Ñ 3氢与相对于所述核碱基扭曲芳环键。该加合物经历Ñ 7 -protonation与电离常数和n计算7质子亲和力（PA）值类似于用于dG的测量。水解动力学表明，C 8-芳基-dG核苷加合物比dG更易于酸催化水解，其中带有对位取代基的k 1值为ca。比k 1大90至200倍对于dG，对原加合物的作用仅约。大9至60倍。通

  DOI：

  10.1021/jo901080w
• 作为产物：
  描述：

  4-甲苯硼酸 、 2'-脱氧鸟苷 在 4-（（1R，3R，5S，7R）-1,3,5-三氮杂-7-磷金刚烷-1-ium-1-基）丁烷-1-磺酸盐 、 palladium diacetate 、 三乙胺 作用下， 以 水 为溶剂， 反应 0.08h， 以79%的产率得到8-(4-methylphenyl)-2'-deoxyguanosine
  参考文献：
  名称：

  新型水溶性磷腈类：铃木-宫浦，Sonogashira和核苷的Heck反应的多功能配体†

  摘要：

  两种新的水溶性磷三氮烯配体已被合成为与Pd（OAc）2络合反应的通用配体，并用于催化水中各种嘌呤和嘧啶卤代核苷的无柱铃木-宫浦交叉偶联。催化系统的水溶性简化了交叉偶合产物的分离，使其仅需过滤，而滤液中的催化活性溶液则循环了八次。通过一锅合成FV-100（一种基于核苷的药物，用于带状疱疹或带状疱疹治疗的3期临床试验），也已建立了针对核苷的新型无铜Sonogashira偶联方案。通过另一种抗病毒药物：BVDU的合成证明了Heck反应的应用。

  DOI：

  10.1039/c6ra19039a

文献信息

• Water-Soluble Pd–Imidate Complexes: Broadly Applicable Catalysts for the Synthesis of Chemically Modified Nucleosides via Pd-Catalyzed Cross-Coupling
  作者：Vijay Gayakhe、Ajaykumar Ardhapure、Anant R. Kapdi、Yogesh S. Sanghvi、Jose Luis Serrano、Luis García、Jose Pérez、Joaquím García、Gregorio Sánchez、Christian Fischer、Carola Schulzke

  DOI：10.1021/acs.joc.5b02475

  日期：2016.4.1

  A broadly applicable catalyst system consisting of water-soluble Pd–imidate complexes has been enployed for the Suzuki–Miyaura cross-coupling of four different nucleosides in water under mild conditions. The efficient nature of the catalyst system also allowed its application in developing a microwave-assisted protocol with the purpose of expediting the catalytic reaction. Preliminary mechanistic studies

  已采用由水溶性Pd-亚氨酸盐络合物组成的广泛适用的催化剂体系，以在温和条件下将水中的四个不同核苷进行Suzuki-Miyaura交叉偶联。催化剂体系的有效性质也使其可用于开发微波辅助规程，以加快催化反应的速度。初步的机理研究，借助催化剂毒性试验和使用电喷雾电离光谱仪进行的化学计量测试，揭示了可能存在同位催化剂体系。
• Efficient One-Step Suzuki Arylation of Unprotected Halonucleosides, Using Water-Soluble Palladium Catalysts
  作者：Elizabeth C. Western、Jonathan R. Daft、Edward M. Johnson、Peter M. Gannett、Kevin H. Shaughnessy

  DOI：10.1021/jo034289p

  日期：2003.8.1

  modification of unprotected halonucleosides is reported herein. Using a catalyst derived from tris(3-sulfonatophenyl)phosphine (TPPTS) and palladium acetate, 8-bromo-2'-deoxyguanosine (8-BrdG) is coupled with arylboronic acids to give 8-aryl-2'-deoxyguanosine adducts (8-ArdG) in excellent yield in a 2:1 water:acetonitrile solvent mixture. The TPPTS ligand was found to be superior to water-soluble alkylphosphines

  修饰核苷以产生药物活性化合物，诱变模型和寡核苷酸结构探针仍然是令人非常感兴趣的。本文报道了未保护的卤代核苷的水相修饰。使用衍生自三（3-磺酰基苯基）膦（TPPTS）和乙酸钯的催化剂，将8-溴2'-脱氧鸟苷（8-BrdG）与芳基硼酸偶合，得到8-芳基-2'-脱氧鸟苷加合物（8 -ArdG）在2：1的水：乙腈溶剂混合物中以优异的收率。对于该偶联反应，发现TPPTS配体优于水溶性烷基膦。偶联化学已扩展到8-溴-2'-脱氧腺苷（8-BrdA）和5-碘-2'-脱氧尿苷（5-IdU），以及核糖核苷8-溴鸟苷和8-溴腺苷。在所有情况下均获得芳基化加合物的良好至优异的收率。使用三（4,6-二甲基-3-磺酰基苯基）膦（TXPTS），可以在室温下不到1小时的时间内完成8-BrdA和5-IdU的Suzuki偶联。该方法学代表了不需要预先保护核苷的卤代核苷芳基化的有效且通用的方法。
• A General Synthesis of C8-Arylpurine Phosphoramidites
  作者：Vorasit Vongsutilers、Jonathan Daft、Kevin Shaughnessy、Peter Gannett

  DOI：10.3390/molecules14093339

  日期：——

  A general scheme for the synthesis of C8-arylpurine phosphoramidites has been developed. C8-Arylation of C8-bromo-2′-deoxyguanosine is the key step and has been achieved through the use of a Suzuki coupling. Since the coupling reaction is conducted under aqueous conditions, it is unnecessary to protect and then deprotect the hydroxyl groups, thus saving several steps and improving overall yields. Once the C8-arylgroup is introduced, the glycosidic bond becomes very sensitive to acid catalyzed cleavage. Protection of the amino groups as the corresponding N,N-dimethylformamidine derivative improves stability of the derivatives. Synthetic C8-arylpurines were successfully used to prepare synthetic oligonucleotides.

  我们开发了一种合成 C8 芳基嘌呤磷酰胺的通用方案。C8-溴-2′-脱氧鸟苷的 C8-芳基化是关键步骤，是通过使用铃木偶联法实现的。由于偶联反应是在水性条件下进行的，因此不需要先保护羟基，然后再去保护羟基，从而节省了多个步骤，提高了总产率。一旦引入 C8 芳基，糖苷键就会对酸催化裂解变得非常敏感。用相应的 N,N-二甲基甲酰胺衍生物保护氨基基团可提高衍生物的稳定性。合成的 C8 芳基嘌呤被成功用于制备合成寡核苷酸。
• Oxidation of a Biomarker for Phenol Carcinogen Exposure: Expanding the Redox Chemistry of 2′-Deoxyguanosine
  作者：Jennifer L. Weishar、Christopher K. McLaughlin、Michael Baker、Wojciech Gabryelski、Richard A. Manderville

  DOI：10.1021/ol8004694

  日期：2008.5.1

  A biomarker for phenolic carcinogen exposure, 8-(4 ''-hydroxyphenyl)-2'-deoxyguanosine, has been found to undergo oxidative coupling in the presence of Na2IrCl6 to afford ortho-ortho C - C-coupled polyphenols through the intermediacy of a phenoxyl radical. One can envision using such unique chemistry to oxidatively couple strands of DNA for the generation of new biomaterials. Our results also demonstrate the potential for phenolic adducts of DNA to undergo further oxidation reactions that may contribute to phenol-mediated cytotoxicity and genotoxicity.
• Different Patterns of Mutagenicity of Arenediazonium Ions in V79 Cells and Salmonella typhimurium TA102: Evidence for Different Mechanisms of Action
  作者：Terence Lawson、Peter M. Gannett、Wai-Ming Yau、Nar S. Dalal、Bela Toth

  DOI：10.1021/jf00058a014

  日期：1995.10

  The edible mushroom Agaricus bisporus contains several arylhydrazines and arenediazonium ions that are genotoxins. The mechanism whereby arylhydrazines and arenediazonium ions are genotoxic is unknown and may be due to the arenediazonium ion itself or to aryl radicals. The reactions of four arenediazonium ions (p-X-C6H5N2+, X = -CH3, -CH2OH, -CH2OCH3, -CO2H) with purine bases, their mutagenicity, their ability to cause DNA damage, and their tendency toward free radical formation have been studied to elucidate the genotoxic species. It is suggested that either the arenediazonium or aryl radical can act as the ultimate genotoxin. Which species is dominant is dependent upon the arenediazonium ion reduction potential. This relationship may be useful in designing future studies of arenediazonium ion genotoxicity.