8-(4-hydroxymethylphenyl)-2'-deoxyguanosine | 161066-04-2

• 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-hydroxymethylphenyl)-2'-deoxyguanosine
• 英文别名: 8-[4-(hydroxymethyl)phenyl]dGuo；2'-Deoxy-8-[4-(hydroxymethyl)phenyl]guanosine；2-amino-9-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-8-[4-(hydroxymethyl)phenyl]-1H-purin-6-one
• CAS: 161066-04-2
• 化学式: C₁₇H₁₉N₅O₅
• 分子量: 373.368
• InChiKey: DJRWBUNYHOJBPU-QJPTWQEYSA-N

物化性质

• 密度：
  1.78±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 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：
  155
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2'-脱氧鸟苷 、 4-(hydroxymethyl)benzenediazonium tetrafluoroborate 在 sodium hydroxide 作用下， 以 水 为溶剂， 反应 24.0h， 以30.6 mg的产率得到8-(4-hydroxymethylphenyl)-2'-deoxyguanosine
  参考文献：
  名称：

  DNA Base and Deoxyribose Modification by the Carbon-Centered Radical Generated from 4-(Hydroxymethyl)benzenediazonium Salt, a Carcinogen in Mushroom

  摘要：

  Modification of the base and the sugar moieties of DNA with 4-(hydroxymethyl)benzenediazonium salt (HMBD), a carcinogen in the mushroom Agaricus bisporus, was investigated. When deoxyribonucleosides dGuo, dAdo, dThd, and dCyd were incubated with HMBD at pH 7.4 and 37 degrees C, the levels of all the nucleosides were decreased. The decrease was inhibited by ethanol or Cys. When deoxyribose was incubated with HMBD, malonaldehyde was released as assessed by the thiobarbituric acid reactivity. The release was inhibited by ethanol. Major products of the reaction of dGuo and dAdo with HMBD were isolated, and their structures were established to be 8-[4-(hydroxymethyl)phenyl]dGuo (8-HMP-dGuo) and 8-[4-(hydroxymethyl)phenyl]dAdo (8-HMP-dAdo), respectively. Calf thymus DNA treated with HMBD was enzymatically digested into nucleosides, in which 8-HMP-dGuo and 8-HMP-dAdo were detected. Formation of the modified nucleosides in DNA was inhibited by ethanol or 2-mercaptoethanol. Malonaldehyde was released from DNA treated with HMBD, which indicated that the deoxyribose moiety of DNA had been damaged. The results indicate that the 4-(hydroxymethyl)phenyl radical generated from HMBD can directly modify the base and the sugar moieties of DNA under the mild conditions. Inhibitory effect of ethanol was ascribable to its scavenging activity for the carbon-centered radical. The inhibitory effect of Cys and 2-mercaptoethanol was found to be due to the formation of the reversible adducts between HMBD and the SH compounds.

  DOI：

  10.1021/tx00045a006

文献信息

• 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。
• 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.
• DNA Base and Deoxyribose Modification by the Carbon-Centered Radical Generated from 4-(Hydroxymethyl)benzenediazonium Salt, a Carcinogen in Mushroom
  作者：Kazuyuki Hiramoto、Masae Kaku、Atsushi Sueyoshi、Mizuko Fujise、Kiyomi Kikugawa

  DOI：10.1021/tx00045a006

  日期：1995.4

  Modification of the base and the sugar moieties of DNA with 4-(hydroxymethyl)benzenediazonium salt (HMBD), a carcinogen in the mushroom Agaricus bisporus, was investigated. When deoxyribonucleosides dGuo, dAdo, dThd, and dCyd were incubated with HMBD at pH 7.4 and 37 degrees C, the levels of all the nucleosides were decreased. The decrease was inhibited by ethanol or Cys. When deoxyribose was incubated with HMBD, malonaldehyde was released as assessed by the thiobarbituric acid reactivity. The release was inhibited by ethanol. Major products of the reaction of dGuo and dAdo with HMBD were isolated, and their structures were established to be 8-[4-(hydroxymethyl)phenyl]dGuo (8-HMP-dGuo) and 8-[4-(hydroxymethyl)phenyl]dAdo (8-HMP-dAdo), respectively. Calf thymus DNA treated with HMBD was enzymatically digested into nucleosides, in which 8-HMP-dGuo and 8-HMP-dAdo were detected. Formation of the modified nucleosides in DNA was inhibited by ethanol or 2-mercaptoethanol. Malonaldehyde was released from DNA treated with HMBD, which indicated that the deoxyribose moiety of DNA had been damaged. The results indicate that the 4-(hydroxymethyl)phenyl radical generated from HMBD can directly modify the base and the sugar moieties of DNA under the mild conditions. Inhibitory effect of ethanol was ascribable to its scavenging activity for the carbon-centered radical. The inhibitory effect of Cys and 2-mercaptoethanol was found to be due to the formation of the reversible adducts between HMBD and the SH compounds.