(2R,3S,5R)-5-[2-氨基-6-(苯基甲氧基)嘌呤-9-基]-2-(羟基甲基)四氢呋喃-3-醇 | 129732-90-7

• 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: (2R,3S,5R)-5-[2-氨基-6-(苯基甲氧基)嘌呤-9-基]-2-(羟基甲基)四氢呋喃-3-醇
• 英文名称: O⁶-Benzyl-2'-deoxyguanosine
• 英文别名: 2'-deoxy-(6-benzyloxy)-guanosine；O6-benzyl-2'-deoxyguanosine；O₆-benzyl-2'-deoxyguanosine；O(6)-Benzyl-2'-deoxyguanosine；(2R,3S,5R)-5-(2-amino-6-phenylmethoxypurin-9-yl)-2-(hydroxymethyl)oxolan-3-ol
• CAS: 129732-90-7
• 化学式: C₁₇H₁₉N₅O₄
• 分子量: 357.369
• InChiKey: MTEDBOAIQUHDQD-YNEHKIRRSA-N

物化性质

• 熔点：
  49-52°C
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  129
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (2R,3S,5R)-5-[2-氨基-6-(苯基甲氧基)嘌呤-9-基]-2-(羟基甲基)四氢呋喃-3-醇 生成 2-fluoro-O⁶-benzyl-2'-deoxyinosine
  参考文献：
  名称：

  Epoxide and diol epoxide adducts of polycyclic aromatic hydrocarbons at the exocyclic amino group of deoxyguanosine

  摘要：

  Synthesis and separation of the diastereomeric trans N2-2'-deoxyguanosine adducts of tetrahydrophenanthrene 3,4-epoxide and benzo[a]pyrene 7,8-diol 9, 10-epoxide (benzylic hydroxyl group and epoxide oxygen trans), as well as the incorporation of the former into the pentanucleotide TpApG*pApT, are described.

  DOI：

  10.1016/s0040-4039(00)92649-2
• 作为产物：
  描述：

  2'-脱氧鸟苷 在 4-二甲氨基吡啶 、 氨 、 三乙胺 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 1,4-二氧六环 、 甲醇 、 乙腈 为溶剂， 反应 0.58h， 生成 (2R,3S,5R)-5-[2-氨基-6-(苯基甲氧基)嘌呤-9-基]-2-(羟基甲基)四氢呋喃-3-醇
  参考文献：
  名称：

  Epoxide and diol epoxide adducts of polycyclic aromatic hydrocarbons at the exocyclic amino group of deoxyguanosine

  摘要：

  Synthesis and separation of the diastereomeric trans N2-2'-deoxyguanosine adducts of tetrahydrophenanthrene 3,4-epoxide and benzo[a]pyrene 7,8-diol 9, 10-epoxide (benzylic hydroxyl group and epoxide oxygen trans), as well as the incorporation of the former into the pentanucleotide TpApG*pApT, are described.

  DOI：

  10.1016/s0040-4039(00)92649-2

文献信息

• <i>N</i>⁶-Arylation of 2‘-Deoxyadenosine via Copper-Catalyzed Direct Coupling with Aryl Halides
  作者：Chongzhao Ran、Qing Dai、Ronald G. Harvey

  DOI：10.1021/jo040284w

  日期：2005.4.1

  A general method for efficient N6-arylation of 2‘-deoxyadenosine via copper-catalyzed direct coupling with aryl iodides and bromides is described. The method is useful for aryl halides with either electron-donating or electron-withdrawing groups.

  描述了一种通过铜催化的与芳基碘化物和溴化物的直接偶联，有效地进行2'-脱氧腺苷的N 6-芳基化的一般方法。该方法可用于具有给电子或吸电子基团的芳基卤化物。
• Strategies for Synthesis of Adducts of <i>o</i>-Quinone Metabolites of Carcinogenic Polycyclic Aromatic Hydrocarbons with 2‘-Deoxyribonucleosides
  作者：Chongzhao Ran、Qing Dai、Qian Ruan、Trevor M. Penning、Ian A. Blair、Ronald G. Harvey

  DOI：10.1021/jo701667u

  日期：2008.2.1

  and the quinone path. The latter involves aldo-keto reductase mediated oxidation of PAH dihydrodiol metabolites to catechols that enter into redox cycles with quinones. This results in generation of reactive oxygen species (ROS) that attack DNA, and the PAH quinones also react with DNA to form adducts. Several strategies for synthesis of the stable adducts formed by the o-quinone metabolites of carcinogenic

  多环芳烃（PAH）是化石燃料，烟草和其他有机物质燃烧过程中产生的主要环境致癌物。目前的证据表明，PAHs可以通过酶转化为活性代谢产物，这些代谢产物与DNA反应形成加合物，从而导致突变。已经提出了三种活化途径：二醇环氧化物途径，自由基阳离子途径和醌途径。后者涉及醛酮还原酶介导的PAH二氢二醇代谢物氧化为儿茶酚，后者与醌进入氧化还原循环。这导致了攻击DNA的活性氧（ROS）的生成，PAH醌也与DNA反应形成加合物。合成由o形成的稳定加合物的几种策略研究并比较了具有2'-脱氧核糖核苷的致癌PAHs的对苯二酚代谢产物。研究的PAH醌为苯并[ a ]蒽-3,4-二酮及其7-甲基和7,12-二甲基衍生物。母体PAHs表现出从无活性到高效的一系列致癌性。设计了两种合成方法，不同的是所使用的催化剂，Pd（OAc）2或CuI。Pd介导的方法涉及将保护的氨基邻苯二酚PAH衍生物与halo-2'-脱氧核糖核苷偶
• <i>O</i>⁶-(Alkyl/aralkyl)guanosine and 2‘-Deoxyguanosine Derivatives:  Synthesis and Ability To Enhance Chloroethylnitrosourea Antitumor Action
  作者：Emmanuelle Mounetou、Eric Debiton、Catherine Buchdahl、Daniel Gardette、Jean-Claude Gramain、Jean-Claude Maurizis、Annie Veyre、Jean-Claude Madelmont

  DOI：10.1021/jm960881d

  日期：1997.8.1

  A series of O6-(alkyl/aralkyl)guanosines and 2'-deoxyguanosine analogs extended to peracetyl and N2-acetyl derivatives, potentially water soluble, was synthesized. Each was associated with N'-(2-chloroethyl)-N-[2-(methylsulfonyl)ethyl]-N'-nitrosourea for in vitro evaluation on M4Beu melanoma cells of their ability to enhance the cytotoxic effect of this chloroethylnitrosourea, which is frequently reduced

  合成了一系列O6-（烷基/芳烷基）鸟苷和2'-脱氧鸟苷类似物，它们扩展到可能具有水溶性的全乙酰基和N2-乙酰基衍生物。每个都与N'-（2-氯乙基）-N- [2-（甲基磺酰基）乙基] -N'-亚硝基脲相关，以体外评估M4Beu黑色素瘤细胞增强该氯代乙基亚硝基脲的细胞毒性作用的能力。通常通过O6-烷基鸟嘌呤-DNA-烷基转移酶进行的修复而减少。结构活性分析表明，（i）苄基和4-卤代苄基是提供显着活性所需的O6-取代基，（ii）2'-脱氧鸟苷衍生物比鸟苷类似物具有更高的效力，（iii）乙酰化，尤其是在N2上位置，通常会产生具有中等能力的化合物，但可能会阻止此类核苷掺入DNA。因此，O6-（4-碘苄基）-N2-乙酰鸟苷（3b）和O6-苄基过乙酰基-2'-脱氧鸟苷（2a）以及O6-苄基-N2-乙酰鸟苷（1b）和O6-苄基-N2-乙酰基到目前为止，水溶性最高的-2'-脱氧鸟苷（2b）具有良好的特性，可用于通过静脉途径进行的进一步体内试验。
• [EN] BETA-GLUGURONIDASE CLEAVABLE PRODRUGS OF O6-ALKYLGUANINE-DNA ALKYLTRANSFERASE INACTIVATORS<br/>[FR] PROMEDICAMENTS A BASE D'AGENTS D'INACTIVATION DE L'O6-ALKYLGUANINE-ADN ALKYLTRANSFERASE, CLIVABLES PAR LA BETA-GLUCURONIDASE
  申请人：US GOV HEALTH & HUMAN SERV

  公开号：WO2006029065A1

  公开（公告）日：2006-03-16

  Disclosed are prodrugs of inactivators of 06-alkylguanine-DNA alkyltransferase (AGT). The prodrugs are cleavable by the (3-glucuronidase enzyme, which is either administered to the patient or produced by necrotic tumor cells. The prodrugs are represented by the formula A-B-C, wherein A is a glucuronosyl residue linked through its 1-oxygen to the phenyl ring of B; B is a benzyloxycarbonyl group, optionally ring­ substituted with one or more electron withdrawing groups; and C is an inactivator of AGT, e.g., a substituted or unsubstituted 06-benzylguanine or 06-benzyl-2'-deoxyguanosine. Also disclosed are pharmaceutical compositions comprising a prodrug and a pharmaceutically acceptable carrier, and a method of use of the prodrugs in enhancing the chemotherapeutic treatment of tumor cells in a mammal, e.g., a human, with an antineoplastic alkylating agent that causes cytotoxic lesions at the 06-position of guanine.

  本发明公开了06-烷基鸟嘌呤-DNA烷基转移酶（AGT）失活剂的前药。这些前药可以被（3-葡萄糖醛酸酶酶）水解，该酶可以被注射到患者体内或由坏死肿瘤细胞产生。前药由公式A-B-C表示，其中A是通过其1-氧原子与B的苯环连接的葡萄糖醛酸残基；B是苄氧羰基基团，可以选择性地被一个或多个电子提取基团取代；而C是AGT的失活剂，例如取代或未取代的06-苄基鸟嘌呤或06-苄基-2'-脱氧鸟苷。本发明还公开了包含前药和药学上可接受的载体的制药组合物，以及在增强哺乳动物（例如人类）中肿瘤细胞的化疗治疗中使用前药的方法，该方法使用一种抗肿瘤烷基化剂，在鸟嘌呤的06位引起细胞毒性损伤。
• Effect of Ionic State of 2‘-Deoxyguanosine and Solvent on Its Aralkylation by Benzyl Bromide
  作者：Ki-Young Moon、Robert C. Moschel

  DOI：10.1021/tx980012m

  日期：1998.6.1

  To extend studies of the aralkylation of nucleic acid components under a variety of solvent conditions, we determined product distributions from the reactions of benzyl bromide with 2'-deoxyguanosine and the anion of 2'-deoxyguanosine in 2,2,2-trifluoroethanol (TFE) and compared these distributions with those from the reaction of the anion with benzyl bromide in N'\N-dimethylacetamide (DMA). 7-Benzylguanine was the only benzylated product detected in the reaction with the neutral nucleoside in TFE, In striking contrast, the reaction of the anion of 2'-deoxyguanosine with benzyl bromide in TFE produced N-2-benzyl-2'-deoxyguanasine in significant yield and with high selectivity. The reaction of the anion of 2'-deoxyguanosine with benzyl bromide in DMA produced products derived only from reaction at the 1- and/or 7-position of the nucleoside. The weakly nucleophilic but protic polar solvent TFE and the iminolate tautomeric form of the 2'-deoxyguanosine anion appear to be essential for benzylation at the exocyclic N-2-position.