8-hydroxy-3-(4-hydroxy-5-hydroxymethyl-tetra-hydrofuran-2-yl)-6-methyl-5,6,7,8-tetrahydro-3H-1,3,4,5,8a-pentaaza-cyclopenta[b]naphthalen-9-one | 132014-87-0

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: 8-hydroxy-3-(4-hydroxy-5-hydroxymethyl-tetra-hydrofuran-2-yl)-6-methyl-5,6,7,8-tetrahydro-3H-1,3,4,5,8a-pentaaza-cyclopenta[b]naphthalen-9-one
• 英文别名: 3-(2-deoxyribos-1-yl)-5,6,7,8-tetrahydro-8-hydroxy-6-methylpyrimido[1,2-a]purine-10(3H)-one；3-(2-deoxyribos-1-yl)-5,6,7,8-tetrahydro-8-hydroxy-6-methylpyrimido[1,2-a]purine-10(3H)one；"a-Methyl-gamma-hydroxy-1,N2-propano-2'-deoxyguanosine(Mixture of Diastereomers)"；8-hydroxy-3-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-methyl-5,6,7,8-tetrahydropyrimido[1,2-a]purin-10-one
• CAS: 132014-87-0
• 化学式: C₁₄H₁₉N₅O₅
• 分子量: 337.335
• InChiKey: DKBDYPZFCQIHPX-AZGGWRLDSA-N

物化性质

• 熔点：
  135-137°C
• 沸点：
  724.7±70.0 °C(Predicted)
• 密度：
  1.93±0.1 g/cm3(Predicted)
• 溶解度：
  甲醇（微溶）、水（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  132
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  8-hydroxy-3-(4-hydroxy-5-hydroxymethyl-tetra-hydrofuran-2-yl)-6-methyl-5,6,7,8-tetrahydro-3H-1,3,4,5,8a-pentaaza-cyclopenta[b]naphthalen-9-one 生成 2'-脱氧鸟苷
  参考文献：
  名称：

  在鸟嘌呤核苷和核苷酸与乙醛反应中平稳，选择性地形成环状1，N 2-丙烷加合物

  摘要：

  在含有碱性氨基酸（如精氨酸和赖氨酸）的pH 8.0磷酸盐缓冲液中，用过量的乙醛处理鸟嘌呤核苷和核苷酸，即使在温和条件下，也能平稳，选择性地形成相应的环状1，N 2-丙烷加合物。

  DOI：

  10.1016/s0040-4039(02)01530-7
• 作为产物：
  描述：

  2'-脱氧鸟苷 、 丁烯-2-醛 在 phosphate buffer 、 L-精氨酸 作用下， 反应 1.0h， 以95%的产率得到8-hydroxy-3-(4-hydroxy-5-hydroxymethyl-tetra-hydrofuran-2-yl)-6-methyl-5,6,7,8-tetrahydro-3H-1,3,4,5,8a-pentaaza-cyclopenta[b]naphthalen-9-one
  参考文献：
  名称：

  A convenient preparative method for the 1,N2-cyclic adducts of guanine nucleosides and nucleotides with crotonaldehyde

  摘要：

  The treatment of guanine nucleosides and nucleotides with excess crotonaldehyde in pH 8.0 phosphate buffer containing an equimolar amount of L-arginine at 50degreesC for 2 h resulted in the selective formation of the corresponding cyclic 1,N-2 -propano adducts as a mixture of its diastercomers. 0 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(02)01047-5

文献信息

• A Schiff Base Is a Major DNA Adduct of Crotonaldehyde
  作者：Mingyao Wang、Edward J. McIntee、Guang Cheng、Yongli Shi、Peter W. Villalta、Stephen S. Hecht

  DOI：10.1021/tx000234w

  日期：2001.4.1

  LC-APCI-MS, and MS/MS. Four isomers of N(2)-(3-hydroxybutylidene)dG were observed. The (R)- and (S)-isomers were identified by reactions of chiral paraldol with dG; each existed as a pair of interconverting (E)- and (Z)-isomers. These data indicate that the structure of the major Schiff base DNA adduct in crotonaldehyde-treated DNA is N(2)-(3-hydroxybutylidene)dG (7). This adduct is unstable at the nucleoside

  先前的研究表明，巴豆醛与DNA的反应会产生迈克尔加成产物，并且已在人体组织以及未经处理的实验动物组织中检测到了这些产物。第二类巴豆醛-DNA加合物在水解时释放出2-（2-羟丙基）-4-羟基-6-甲基-1,3-二恶烷（paraldol，12），这些加合物在数量上比迈克尔加成更重要体外。在这项研究中，我们证明巴豆醛释放帕拉尔多的DNA加合物的主要来源是席夫碱。巴豆醛与DNA的反应，然后用NaBH（3）CN处理和酶水解，导致形成N（2）-（3-羟丁基）dG（10），通过其UV，MS和质子NMR鉴定。巴豆醛或对苯二酚与dG的反应表明，席夫碱对N（2）-（3-羟基丁基）dG的前体是N（2）-（3-羟基丁烯）dG（7），通过UV，LC-APCI-MS鉴定，以及MS / MS。观察到N（2）-（3-羟基丁烯）dG的四个异构体。（R）-和（S）-异构体通过手性对羟基苯酚与dG的反应鉴定。每个都以一对互变的
• Identification of DNA Adducts of Acetaldehyde
  作者：Mingyao Wang、Edward J. McIntee、Guang Cheng、Yongli Shi、Peter W. Villalta、Stephen S. Hecht

  DOI：10.1021/tx000118t

  日期：2000.11.1

  anosine (11). Adduct 9 has been previously identified in reactions of crotonaldehyde with DNA. However, the distribution of diastereomers was different in the acetaldehyde and crotonaldehyde reactions, indicating that the formation of 9 from acetaldehyde does not proceed through crotonaldehyde. Adduct 12 is an interstrand cross-link. Although previous evidence indicates the formation of cross-links

  乙醛是一种诱变剂和致癌物，在人类环境中广泛存在，有时数量很多，但对其与DNA的反应知之甚少。在这项研究中，我们确定了三种新型的稳定乙醛DNA加合物，包括链间交联。这些是除先前表征的N（2）-亚乙基二氧鸟苷之外形成的。使乙醛与小牛胸腺DNA或脱氧鸟苷反应。分离出DNA，并进行酶水解。在某些情况下，首先用NaBH（3）CN处理DNA。通过HPLC分析反应混合物，并分离加合物并通过UV，（1）H NMR和MS表征。主要的加合物是N（2）-乙二氧基脱氧鸟苷（1），经NaBH（3）CN处理DNA后被鉴定为N（2）-乙基脱氧鸟苷（7）。新的乙醛加合物是3-（2-脱氧核糖-1-基）-5,6,7，8-四氢-8-羟基-6-甲基嘧啶[1,2-a]嘌呤-10（3H）one（9 ），3-（2-deoxyribos-1-yl）-5,6,7,8-tetrahydro-8-（N（2）-deoxyguanosyl + ++）-6-methylpyrimido
• Metabolic Profiling of Chronic Cadmium Exposure in the Rat
  作者：Julian L. Griffin、Lee A. Walker、Richard F. Shore、Jeremy K. Nicholson

  DOI：10.1021/tx015521u

  日期：2001.10.1

  A confounding problem with studying the effects of environmental exposure to contaminants in wild populations is that analytical techniques are invasive, particularly where the physiological effects of the toxin are assessed. In this study, a metabonomic approach to investigate the biochemical effects of chronic oral exposure to environmentally realistic doses of CdCl2 (low, 8 mg/kg; high, 40 mg/kg) is presented. H-1 NMR spectra of urine from exposed animals were analyzed using pattern recognition methods to identify biomarkers for a 94 day exposure period. Creatinuria and both increased excretion and complexation of citrate was detected after 19 days of exposure in both exposure groups. This was accompanied by a decrease in plasma Ca2+/Mg2+ ratio in blood plasma after 94 days. Post mortem, magic angle spinning (MAS) H-1 NMR spectroscopy was used alongside conventional analytical techniques to investigate intact tissue directly. According to atomic absorption sectroscopy, kidney tissue accumulated 26.8 +/- 2.5 mug of Cd2+/g dry wt (low) and 75.9 +/- 4.3 mug of Cd2+/g dry wt (high). Using high-resolution MAS H-1 NMR spectroscopy altered lipid content was detected in kidneys from animals exposed to Cd2+. However, unlike acute exposure, no testicular damage was evident. This systemic approach to metabolism demonstrated the different physiological effects of chronic subacute compared with an acute exposure to Cd2+.
• [¹³C₂]- Acetaldehyde Promotes Unequivocal Formation of 1,<i>N</i>²-Propano-2′-deoxyguanosine in Human Cells
  作者：Camila Carrião M. Garcia、José Pedro F. Angeli、Florêncio P. Freitas、Osmar F. Gomes、Tiago F. de Oliveira、Ana Paula M. Loureiro、Paolo Di Mascio、Marisa H. G. Medeiros

  DOI：10.1021/ja2004686

  日期：2011.6.22

  Acetaldehyde is an environmentally widespread genotoxic aldehyde present in tobacco smoke, vehicle exhaust and several food products. Endogenously, acetaldehyde is produced by the metabolic oxidation of ethanol by hepatic NAD-dependent alcohol dehydrogenase and during threonine catabolism. The formation of DNA adducts has been regarded as a critical factor in the mechanisms of acetaldehyde mutagenicity and carcinogenesis. Acetaldehyde reacts with 2'-deoxyguanosine in DNA to form primarily N-2-ethylidene-2'-deoxyguanosine. The subsequent reaction of N-2-ethylidenedGuo with another molecule of acetaldehyde gives rise to 1,N-2-propano-2'-deoxyguanosine (1,N-2-propanodGuo), an adduct also found as a product of the crotonaldehyde reaction with dGuo. However, adducts resulting from the reaction of more than one molecule of acetaldehyde in vivo are still controversial. In this study, the unequivocal formation of 1,N-2-propanodGuo by acetaldehyde was assessed in human cells via treatment with [C-13(2)]-acetaldehyde. Detection of labeled 1,N-2-propanodGuo was performed by HPLC/MS/MS. Upon acetaldehyde exposure (703 mu M), increased levels of both 1,N-2-etheno-2'-deoxyguanosine (1,N-2-epsilon dGuo), which is produced from alpha,beta-unsaturated aldehydes formed during the lipid peroxidation process, and 1,N-2-propanodGuo were observed. The unequivocal formation of 1,N-2-propanodGuo in cells exposed to this aldehyde can be used to elucidate the mechanisms associated with acetaldehyde exposure and cancer risk.
• Oxidative hydrolysis of a cyclic 1,N2-propano-2′-deoxyguanosine, an adduct of 2′-deoxyguanosine with acetaldehyde or crotonaldehyde
  作者：Magoichi Sako、Shinsuke Inagaki、Yukihiro Esaka、Yoshihiro Deyashiki

  DOI：10.1016/s0040-4039(03)01864-1

  日期：2003.9

  The SO4.--oxidation of cyclic 1,N-2-propano-2'-deoxyguanosine, chemo- and regioselectively produced in the reaction of 2'-deoxyguanosine with excessive acetaldehyde or crotonaldehyde, resulted in the smooth formation of (4-hydroxy-5hydroxymethyltetrahydrofuran-2-ylimino)-(4-hydroxy-6-methyltetrahydropyrimidin-2-ylideneamino)acetic acid, 3-(4-hydroxy-5-hydroxymethyltetrahydrofuran-2-yl)-6-methyl-3H-1,3,4,5,8a-pentaazacyclopenta[b]naphthalen-9-one, and 2'-deoxyguanosine even under neutral conditions. The formation of the guanine-ring opened product during the reaction is very interesting and appears to closely relate to the mechanisms for the point-mutations of DNA by these mutagenic and carcinogenic aldehydes. (C) 2003 Elsevier Ltd. All rights reserved.