(2R,3R,4S,5R)-2-(6-cyclobutyl-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol | 1356830-31-3

• 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: (2R,3R,4S,5R)-2-(6-cyclobutyl-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol
• 英文别名: 6-cyclobutyl-9-(β-D-ribofuranosyl)purine；(2R,3R,4S,5R)-2-(6-cyclobutylpurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 1356830-31-3
• 化学式: C₁₄H₁₈N₄O₄
• 分子量: 306.321
• InChiKey: DOCSLZVJYCDMNZ-LHNIVKCTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2,3,5-三-O-乙酰基-6-氯嘌呤-9-β-D-呋喃核糖苷 在 甲醇 、 氨 、 magnesium 作用下， 以 四氢呋喃 为溶剂， 反应 7.0h， 生成 (2R,3R,4S,5R)-2-(6-cyclobutyl-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2011.10.039

文献信息

• Synthesis of C6-Substituted Purine Nucleoside Analogues via Late-Stage Photoredox/Nickel Dual Catalytic Cross-Coupling
  作者：James J. Perkins、Valerie W. Shurtleff、Alayna M. Johnson、Abdellatif El Marrouni

  DOI：10.1021/acsmedchemlett.0c00673

  日期：2021.4.8

  Nucleoside analogues have been and continue to be extremely important compounds in drug discovery. Despite the significant effort dedicated to their synthesis, medicinal chemistry campaigns around these structures are often hampered by synthetic challenges. We describe a strategy for the functionalization of purine nucleosides via photoredox and nickel-catalyzed sp2–sp3 cross-coupling. The conditions

  核苷类似物一直是并将继续是药物发现中极其重要的化合物。尽管为它们的合成付出了巨大的努力，但围绕这些结构的药物化学活动经常受到合成挑战的阻碍。我们描述了一种通过光氧化还原和镍催化的 sp 2 -sp 3交叉偶联对嘌呤核苷进行功能化的策略。本文描述的条件允许未受保护的核苷与容易获得的烷基溴偶联，为它们在平行药物化学中的应用提供了机会。
• 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.