6-methyl-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)purine | 52921-35-4

• 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: 6-methyl-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)purine
• 英文别名: 9-(2,3,5-Tri-O-acetyl-β-D-ribofuranosyl)-6-methyl-purin；[(2R,3R,4R,5R)-3,4-diacetyloxy-5-(6-methylpurin-9-yl)oxolan-2-yl]methyl acetate
• CAS: 52921-35-4
• 化学式: C₁₇H₂₀N₄O₇
• 分子量: 392.368
• InChiKey: OLGDOWZBOORTRW-DNNBLBMLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  132
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  6-methyl-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)purine 在 甲胺 作用下， 生成 (2R,3s,4r,5r)-2-(羟基甲基)-5-(6-甲基-9h-嘌呤-9-基)四氢呋喃-3,4-二醇
  参考文献：
  名称：

  邻苯二酚-O-甲基转移酶（COMT）活性位点上的分子识别：双底物抑制剂中的腺嘌呤替代。

  摘要：

  L- Dopa是帕金森氏病的标准治疗药物，可被儿茶酚-O-甲基转移酶（COMT）灭活。COMT催化活化的甲基从S腺苷甲硫氨酸（SAM）转移到其邻苯二酚底物，例如L-多巴，存在镁离子。对COMT SAM结合位点的分子识别特性仅进行了稀疏的研究。在这里，我们通过双底物抑制剂的腺嘌呤部分的结构改变来探索该位点。由于该核碱基在生物系统中的丰富性和重要性，对腺嘌呤的分子识别特别受关注。新型的腺嘌呤替代双底物抑制剂是通过基于结构的设计开发的，并使用了由Vorbrüggen及其同事引入的核苷化方案进行合成。用放射化学测定法测量腺嘌呤部分与COMT的关键相互作用。几种双底物抑制剂，最著名的是腺嘌呤替代品硫代吡啶，嘌呤，N对于低至6 n M的COMT ，甲基腺嘌呤和6甲基嘌呤显示出纳摩尔的IC 50值（中位抑制浓度）。与COMT和Mg 2+形成三元复合物的双底物抑制剂的一系列六个共晶体结构证实了我们预测的腺

  DOI：

  10.1002/chem.201003648
• 作为产物：
  描述：

  6-mesyloxymethyl-9-2',3',5'-tri-O-acetyl-β-D-ribofuranosylpurine 在 sodium tetrahydroborate 、 sodium iodide 作用下， 以 甲醇 、 丙酮 为溶剂， 反应 4.25h， 生成 6-methyl-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)purine
  参考文献：
  名称：

  Shimazaki, Masami; Nakamura, Hikaru; Iitaka, Yoichi, Chemical and pharmaceutical bulletin, 1983, vol. 31, # 9, p. 3104 - 3112

  摘要：

  DOI：

文献信息

• Antiviral activity of C-alkylated purine nucleosides obtained by cross-coupling with tetraalkyltin reagents
  作者：Arthur A. Van Aerschot、Petros Mamos、Nancy J. Weyns、Satoru Ikeda、Erik De Clercq、Piet A. Herdewijn

  DOI：10.1021/jm00072a013

  日期：1993.10

  2-, 6-, And 8-alkylated (methyl, ethyl, and vinyl) adenosine analogues were synthesized by a palladium-catalyzed cross-coupling of a tetraalkyltin with the halogenated purine nucleosides. The synthesis of the 8-substituted analogues was accomplished using a transient protection procedure. The 6-alkylated-9-beta-D-ribofuranosylpurines as well as 2-ethyladenosine were cytotoxic at relatively low concentrations

  通过将四烷基锡与卤代嘌呤核苷进行钯催化的交叉偶联，可合成2-，6-和8-烷基化（甲基，乙基和乙烯基）的腺苷类似物。8-取代类似物的合成使用瞬态保护程序完成。6烷基化的9-β-D-呋喃呋喃糖基嘌呤以及2-乙基腺苷在相对较低的浓度（0.8-10微克/ mL）下具有细胞毒性。8-甲基腺苷是牛痘病毒的有效和选择性抑制剂，而8-乙基和8-乙烯基腺苷对呼吸道合胞病毒具有特异性抑制作用。8-Vinyladenosine显示出对单纯疱疹病毒（1型）的特殊活性。
• Convenient Syntheses of 6-Methylpurine and Related Nucleosides
  作者：Abdalla E. A. Hassan、Reham A. I. Abou-elkair、John A. Montgomery、John A. Secrist

  DOI：10.1080/15257770008035035

  日期：2000.7

  Efficient methods for the synthesis of 6-methylpurine (3), 9-(2-deoxy-beta-D-erythro-pentofuranosyl)-6-methylpurine (8), and 6-methyl-9-beta-D-ribofuranosylpurine (5) are described. Methodology involving the (Ph3P)4Pd catalyzed cross-coupling reaction of CH3ZnBr with several different 6-chloropurine derivatives is described in high yield. This methodology now provides a facile and high-yielding synthesis

  合成6-甲基嘌呤（3），9-（2-脱氧-β-D-赤五戊呋喃糖基）-6-甲基嘌呤（8）和6-甲基-9-β-D-核呋喃呋喃糖基嘌呤的有效方法（5 ）进行了说明。以高收率描述了涉及CH3ZnBr与几种不同的6-氯嘌呤衍生物的（Ph3P）4Pd催化交叉偶联反应的方法。现在，该方法学提供了8的简便且高产率的合成方法，对于癌症基因治疗的研究而言，这是大量所需的。
• Synthesis and evaluation of the substrate activity of C-6 substituted purine ribosides with E. coli purine nucleoside phosphorylase: Palladium mediated cross-coupling of organozinc halides with 6-chloropurine nucleosides
  作者：Abdalla E.A. Hassan、Reham A.I. Abou-Elkhair、James M. Riordan、Paula W. Allan、William B. Parker、Rashmi Khare、William R. Waud、John A. Montgomery、John A. Secrist

  DOI：10.1016/j.ejmech.2011.10.039

  日期：2012.1

  A series of C-6 alkyl, cycloalkyl, and aryl-9-(beta-D-ribofuranosyl)purines were synthesized and their substrate activities with Escherichia colt purine nucleoside phosphorylase (E. coli PNP) were evaluated. (Ph3P)(4)Pd-mediated cross-coupling reactions of 6-chloro-9-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-purine (6) with primary alkyl (Me, Et, n-Pr, n-Bu, isoBu) zinc halides followed by treatment with NH3/MeOH gave the corresponding 6-alkyl-9-(beta-D-ribofuranosyl)purine derivatives 7-11, respectively, in good yields. Reactions of 6 with cycloalkyl(propyl, butyl, pentyl)zinc halides and aryl (phenyl, 2-thienyl)zinc halides gave under similar conditions the corresponding 6-cyclopropyl, cyclobutyl, cyclopentyl, phenyl, and thienyl -9-(beta-D-ribofuranosyl)purine derivatives 12-16, respectively in high yields. E. colt PNP showed a high tolerance to the steric and hydrophobic environment at the 6-position of the synthesized purine ribonucleosides. Significant cytotoxic activity was observed for 8, 12, 15, and 16. Evaluation of 12 and 16 against human tumor xenografts in mice did not demonstrate any selective antitumor activity. In addition, 6-methyl-9-(beta-D-arabinofuranosyl)purine (18) was prepared and evaluated. (C) 2011 Elsevier Masson SAS. All rights reserved.
• Nucleic acid related compounds. 48. Photoaddition of methanol to 9-(.beta.-D-ribofuranosyl) purine (nebularine) to give inhibitors of adenosine deaminase.
  作者：Diederik K. Buffel、Christopher McGuigan、Morris J. Robins

  DOI：10.1021/jo00215a014

  日期：1985.7