2,6-diamino-9-(2,3-dideoxy-β-L-ribofuranosyl)purine

• 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: 2,6-diamino-9-(2,3-dideoxy-β-L-ribofuranosyl)purine
• 英文别名: [(2R,5S)-5-(2,6-diaminopurin-9-yl)tetrahydrofuran-2-yl]methanol；[(2R,5S)-5-(2,6-diaminopurin-9-yl)oxolan-2-yl]methanol
• 化学式: C₁₀H₁₄N₆O₂
• 分子量: 250.26
• InChiKey: OABUIHOVHQHUAO-RITPCOANSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  125
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2,6-dichloro-9-<5-O-(tert-butyldimethylsilyl)-2,3-dideoxy-β-L-ribofuranosyl>purine 在 lithium aluminium tetrahydride 、 叠氮化锂 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 为溶剂， 反应 3.5h， 生成 2,6-diamino-9-(2,3-dideoxy-β-L-ribofuranosyl)purine
  参考文献：
  名称：

  Synthesis of a Series of Purine 2′,3′-Dideoxy-L-Nucleoside Analogues as Potential Antiviral Agents

  摘要：

  Various 2',3'-dideoxy-L-nucleoside analogues, 6-amino-9-(2,3-dideoxy-beta-L-ribofuranosy))purine (19), 2-chloro-6-amino-9-(2,3-dideoxy-beta-L-ribofuranosyl)-purine (20), 2-chloro-6-amino-9-(2,3-dideoxy-4-thio-beta-L-ribofuranosyl)purine (21), 2,5- diamino 9-(2,3-dideoxy-beta-L-ribofuranosyl)purine (26), 2,6-diamino-9-(2,3-dideoxy-4-thio-beta-L-ribofuranosyl)-purine (27), 2-amino-6-chloro-9-(2,3-dideoxy-beta-L-ribofuranosyl)purine (28), (6-chloro-9-(2,3-dideoxy-4-thio-beta-L-ribofuranosyl)purine (29), and 6-amino-9-(2,3-dideoxy-4-thio-beta-L-ribofuranosyl)purine (30) have been synthesized by coupling of the sodium salt of 2-amino-6-chloropurine (1), 6-chloropurine (2), and 2,6-dichloropurine urine (3) with 1-O-acetyl-5-O-(tert-butyldimethylsilyl)-2,3-dideoxy-L-ribofuranose (4) or 1-O-acetyl-5-O-(tert-butyldiphenylsilyl)-2,3-dideoxy-4-thio-L-ribofuranose (5) in anhydrous MeCN in the presence of either EtAlCl(2) or Et(2)AlCl followed by separation of the alp-anomers and deprotection of the blocking groups. However, the synthesis of 9-(2,3-dideoxy-beta-L-ribofuranosyl)guanine (57, beta-L-ddG) was not straightforward. Coupling of the silylated N-2-palmitoylguanine (48) with sugar 4 in anhydrous MeCN, using trimethylsilyl trifluoromethanesulfonate as a catalyst yielded N-9-beta- and N-9-alpha-; N-7-beta- and N-7-alpha-isomers, compounds 49-52, which were separated by silica gel column chromatography with two appropriate eluting solvent systems. Removal of the protecting groups gave compound 57 (beta-L-ddC) and the other 3 related isomers (58-60). The 2',3'-dideoxy-L-nucleoside analogues were tested in vitro against HIV-1, HBV, L1210, P388, S-180, and CCRF-CEM. 6-Amino-9-(2,3-dideoxy-beta-L-ribofuranosyl)purine (19, beta-L-ddA) was found to have antiviral activity against HBV with an ED(50) value of 6 mu M.

  DOI：

  10.1080/15257779508009755

文献信息

• Synthesis of a Series of Purine 2′,3′-Dideoxy-L-Nucleoside Analogues as Potential Antiviral Agents
  作者：Tai-Shun Lin、Mei-Zhen Luo、Ju-Liang Zhu、Mao-Chin Liu、Yong-Lian Zhu、Ginger E. Dutschman、Yung-Chi Cheng

  DOI：10.1080/15257779508009755

  日期：1995.10

  Various 2',3'-dideoxy-L-nucleoside analogues, 6-amino-9-(2,3-dideoxy-beta-L-ribofuranosy))purine (19), 2-chloro-6-amino-9-(2,3-dideoxy-beta-L-ribofuranosyl)-purine (20), 2-chloro-6-amino-9-(2,3-dideoxy-4-thio-beta-L-ribofuranosyl)purine (21), 2,5- diamino 9-(2,3-dideoxy-beta-L-ribofuranosyl)purine (26), 2,6-diamino-9-(2,3-dideoxy-4-thio-beta-L-ribofuranosyl)-purine (27), 2-amino-6-chloro-9-(2,3-dideoxy-beta-L-ribofuranosyl)purine (28), (6-chloro-9-(2,3-dideoxy-4-thio-beta-L-ribofuranosyl)purine (29), and 6-amino-9-(2,3-dideoxy-4-thio-beta-L-ribofuranosyl)purine (30) have been synthesized by coupling of the sodium salt of 2-amino-6-chloropurine (1), 6-chloropurine (2), and 2,6-dichloropurine urine (3) with 1-O-acetyl-5-O-(tert-butyldimethylsilyl)-2,3-dideoxy-L-ribofuranose (4) or 1-O-acetyl-5-O-(tert-butyldiphenylsilyl)-2,3-dideoxy-4-thio-L-ribofuranose (5) in anhydrous MeCN in the presence of either EtAlCl(2) or Et(2)AlCl followed by separation of the alp-anomers and deprotection of the blocking groups. However, the synthesis of 9-(2,3-dideoxy-beta-L-ribofuranosyl)guanine (57, beta-L-ddG) was not straightforward. Coupling of the silylated N-2-palmitoylguanine (48) with sugar 4 in anhydrous MeCN, using trimethylsilyl trifluoromethanesulfonate as a catalyst yielded N-9-beta- and N-9-alpha-; N-7-beta- and N-7-alpha-isomers, compounds 49-52, which were separated by silica gel column chromatography with two appropriate eluting solvent systems. Removal of the protecting groups gave compound 57 (beta-L-ddC) and the other 3 related isomers (58-60). The 2',3'-dideoxy-L-nucleoside analogues were tested in vitro against HIV-1, HBV, L1210, P388, S-180, and CCRF-CEM. 6-Amino-9-(2,3-dideoxy-beta-L-ribofuranosyl)purine (19, beta-L-ddA) was found to have antiviral activity against HBV with an ED(50) value of 6 mu M.