1-[(2R,4S,5R)-5-azido-4-hydroxy-5-(hydroxymethyl)tetrahydrothiophen-2-yl]-5-methyl-pyrimidine-2,4-dione | 1017605-01-4

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物
• 英文名称: 1-[(2R,4S,5R)-5-azido-4-hydroxy-5-(hydroxymethyl)tetrahydrothiophen-2-yl]-5-methyl-pyrimidine-2,4-dione
• 英文别名: 1-[(2R,4S,5R)-5-azido-4-hydroxy-5-(hydroxymethyl)thiolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 1017605-01-4
• 化学式: C₁₀H₁₃N₅O₄S
• 分子量: 299.31
• InChiKey: RKILBWCLZSHKTF-NYNCVSEMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  130
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1-[5-O-acetyl-4-azido-2-deoxy-β-D-erythro-4-thiopentofuranosyl]thymine 在 氨 作用下， 以 甲醇 为溶剂， 反应 6.0h， 以79%的产率得到1-[(2R,4S,5R)-5-azido-4-hydroxy-5-(hydroxymethyl)tetrahydrothiophen-2-yl]-5-methyl-pyrimidine-2,4-dione
  参考文献：
  名称：

  Synthesis and Anti-HIV Activity of 4′-Substituted 4′-Thiothymidines: A New Entry Based on Nucleophilic Substitution of the 4′-Acetoxy Group

  摘要：

  Diacetoxylation of 1-(2,5-dideoxy-beta-L-glycero-pent-4-eno-4-thiofuranosyl)thymine (13) with Pb(OAc)(4) allowed introduction of an acetoxy leaving group to the 4 '-position. Nucleophilic substitution of the resulting 4 '-acetoxy derivative (14) with silicon reagents enabled us to prepare the 4 '-phenylthio (17a), 4 '-azido (18a), 4 '-methoxy (20a), and 4 '-allyl (21a) analogues of 4 '-thiothymidine. 4 '-Cyano (25a) and 4 '-ethynyl (31) nucleosides were also synthesized from 3 ',5 '-bis-O-TBDMS derivative (24). Among novel 4 '-substituted 4 '-thiothymidines, the 4 '-azido (33), 4 '-cyano (36), and 4 '-ethynyl (37) derivatives were found to show potent inhibitory activity against HIV-1 and HIV-2. It is noteworthy that 36 and 37 were also inhibitory against replication of HIV variant resistant to 3TC (HIV-1(M184V)), being as potent as against HIV-1(IIIB).

  DOI：

  10.1021/jm070824s