(2R,3R,4S,5R)-2-(2-amino-6-(ethylthio)-9H-purin-9-yl)-5-(hydroxymethyl)-tetrahydrofuran-3,4-diol | 56964-84-2

• 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-(2-amino-6-(ethylthio)-9H-purin-9-yl)-5-(hydroxymethyl)-tetrahydrofuran-3,4-diol
• 英文别名: (2R,3R,4S,5R)-2-(2-amino-6-ethylsulfanylpurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 56964-84-2
• 化学式: C₁₂H₁₇N₅O₄S
• 分子量: 327.364
• InChiKey: DGWWZVIRZLXJCZ-IOSLPCCCSA-N

物化性质

• 沸点：
  732.9±70.0 °C(Predicted)
• 密度：
  1.88±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  165
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (2R,3R,4S,5R)-2-(2-amino-6-(ethylthio)-9H-purin-9-yl)-5-(hydroxymethyl)-tetrahydrofuran-3,4-diol 在 间氯过氧苯甲酸 作用下， 以 水 、 乙腈 为溶剂， 以63 %的产率得到(2R,3R,4S,5R)-2-(2-amino-6-(ethylsulfonyl)-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol
  参考文献：
  名称：

  10.1002/chem.202401774

  摘要：

  We present herein a novel photo‐mediated homolytic C‐S bond formation for the preparation of alkylthiopurines and alkylthiopurine nucleosides. Despite the presence of reactive sites for the Minisci reaction, chemoselective S‐alkylation remained the predominant pathway. This method allows for the late‐stage introduction of a broad spectrum of alkyl groups onto the sulfur atom of unprotective mercaptopurine derivatives, encompassing 2‐, 6‐, and 8‐mercaptopurine rings. Organoborons serve as efficient and eco‐friendly alkylating reagents, providing advantages in terms of readily availability, stability, and reduced toxicity. Further derivatization of the thioetherified nucleosides, together with anti‐tumor assays, led to the discovery of potent anti‐tumor agents with an IC50 value reaching 6.1 µM (Comp. 31 for Jurkat).

  DOI：

  10.1002/chem.202401774
• 作为产物：
  描述：

  6-氯鸟嘌呤核苷 在 ammonium peroxydisulfate 、 9-mesityl-10-methylacridinium tetrafluoroborate 、 邻苯二酚 、 硫脲 作用下， 以 乙醇 、 水 为溶剂， 反应 18.0h， 生成 (2R,3R,4S,5R)-2-(2-amino-6-(ethylthio)-9H-purin-9-yl)-5-(hydroxymethyl)-tetrahydrofuran-3,4-diol
  参考文献：
  名称：

  10.1002/chem.202401774

  摘要：

  We present herein a novel photo‐mediated homolytic C‐S bond formation for the preparation of alkylthiopurines and alkylthiopurine nucleosides. Despite the presence of reactive sites for the Minisci reaction, chemoselective S‐alkylation remained the predominant pathway. This method allows for the late‐stage introduction of a broad spectrum of alkyl groups onto the sulfur atom of unprotective mercaptopurine derivatives, encompassing 2‐, 6‐, and 8‐mercaptopurine rings. Organoborons serve as efficient and eco‐friendly alkylating reagents, providing advantages in terms of readily availability, stability, and reduced toxicity. Further derivatization of the thioetherified nucleosides, together with anti‐tumor assays, led to the discovery of potent anti‐tumor agents with an IC50 value reaching 6.1 µM (Comp. 31 for Jurkat).

  DOI：

  10.1002/chem.202401774

文献信息

• Pd/PTABS: Low-Temperature Thioetherification of Chloro(hetero)arenes
  作者：Siva Sankar Murthy Bandaru、Shatrughn Bhilare、Jesvita Cardozo、Nicolas Chrysochos、Carola Schulzke、Yogesh S. Sanghvi、Krishna Chaitanya Gunturu、Anant R. Kapdi

  DOI：10.1021/acs.joc.9b00840

  日期：2019.7.19

  Heteroarenes of commercial relevance such as purines and pyrimidines were also found to be useful substrates for the reported transformation. The commercial drug Imuran (azathioprine) was synthesized as an example, and its preparation could be optimized. DFT studies were performed to understand the electronic effects of the tested ligands on the catalytic reaction.

  杂芳基氯化物的硫醚化是必不可少的合成方法，可用于获得生物活性药物和农药。由于它们的（实际或潜在的）工业重要性，出于经济和生态方面的原因，需要开发一种有效的低温协议来获取这些化合物。因此，开发了一种仅在50°C下使用Pd / PTABS系统的高效催化方案。高效率地进行了氯杂芳烃与各种反应性较低的芳基硫醇和烷基硫醇之间的偶联。还发现具有商业意义的杂芳烃，例如嘌呤和嘧啶，是报道的转化的有用底物。以合成的商品药物Imuran（硫唑嘌呤）为例，可以优化其制备方法。