6-cyclopentyl nebularine | 127946-64-9

• 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-cyclopentyl nebularine
• 英文别名: (2R,3R,4S,5R)-2-(6-cyclopentylpurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 127946-64-9
• 化学式: C₁₅H₂₀N₄O₄
• 分子量: 320.348
• InChiKey: JQQOLLDDKJUESI-QGMIFYJMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 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 、 palladium 10% on activated carbon 、 氢气 、 Ammonium hydroxide 、 [双(三氟乙酰氧基)碘]苯 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 反应 17.5h， 生成 6-cyclopentyl nebularine
  参考文献：
  名称：

  无金属、光介导、位点特异性、自由基 C6-H 嘌呤与醇的烷基化，草酸盐介入，无催化剂

  摘要：

  报告了一种温和实用的方案，用于在蓝色 LED 照射下草酸盐干预嘌呤与醇的高度区域选择性 C6-H 烷基化。这种转化不需要过渡金属催化剂，对水分不敏感，也不需要N 2保护。此外，该方法显示出广泛的功能组兼容性并且易于放大。

  DOI：

  10.1002/ejoc.202201491

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。
• Metal-free direct C-6–H alkylation of purines and purine nucleosides enabled by oxidative homolysis of 4-alkyl-1,4-dihydropyridines at room temperature
  作者：Qingsong Jiang、Xiguang Liu、Weili Wang、Yiwen Chen、Mingwu Yu

  DOI：10.1039/d2ob02070j

  日期：——

  Herein we report the application of 4-alkyl-1,4-dihydropyridines (DHPs), which are easily prepared from inexpensive aldehydes in one step, for the direct site-specific C–H alkylation of purines and purine nucleosides. Despite there being three active C(sp2)–H bonds (C-2–H, C-6–H, and C-8–H) in the structure, the reactions still show high regioselectivity at the purinyl C-6–H position. Importantly,

  在这里，我们报告了 4-烷基-1,4-二氢吡啶 (DHP) 的应用，它很容易从廉价的醛一步制备，用于嘌呤和嘌呤核苷的直接位点特异性 C-H 烷基化。尽管结构中存在三个活性 C(sp 2 )–H 键（C-2–H、C-6–H 和 C-8–H），但反应在嘌呤基 C-6– 处仍显示出高区域选择性H位置。重要的是，该反应成功地避免了使用过渡金属催化剂和额外的酸。同时，这些协议对水分不敏感，只需要过硫酸盐作为氧化剂。此外，该方法具有广泛的功能组兼容性，易于放大。值得注意的是，药用嘌呤，例如从担子菌中分离出的天然产物 6-hydroxymethyl nebularine 可以使用该协议顺利制备。
• Light, metal‐free regioselective<scp>C⁶‐H</scp>alkylation of purines and purine nucleosides with alcohols
  作者：Xiguang Liu、Xiangbin Sun、Weili Wang、Miao Tian、Yiwen Chen、Chunhui Zou、Mingwu Yu

  DOI：10.1002/jhet.4659

  日期：2023.7

  A metal-, light-free radical alkylation reaction of purines and nucleosides has been achieved with readily available alcohols (1°, 2°, 3°) as the alkyl radical sources enabled by oxalates, which does not need any catalysts, N2 protection, and protecting groups. Although there are three potential active C(sp2)H bonds and four interferential nitrogen atoms in the purine motif, the reaction still shows

  以草酸盐为烷基自由基源，以易得的醇（1°、2°、3°）实现了嘌呤和核苷的金属、光自由基烷基化反应，不需要任何催化剂、N 2保护和保护基团。尽管嘌呤基序中存在3个潜在的活性C( sp 2 )  H键和4个干扰氮原子，但该反应在C 6  H位上仍然表现出优异的区域选择性，并且不存在多烷基化问题。此外，该方法表现出广泛的功能组耐受性，并且可扩展至克级，可应用于后期 C 嘌呤的 H 烷基化合成具有抗 CEM 活性的 6-环戊基星云碱，从而证明了其实用性。
• 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.
• Regiospecificity C(sp²)–C(sp³) Bond Construction between Purines and Alkenes to Synthesize C⁶-Alkylpurines and Purine Nucleosides Using O₂ as the Oxidant
  作者：Mingwu Yu、Qingsong Jiang、Xiguang Liu、Yiwen Chen、Kai Sun、Miao Tian、Weili Wang

  DOI：10.1021/acs.joc.2c02277

  日期：2023.2.3