1-[4-O-acetoxy-5-O-acetyl-3-O-(tert-butyldimethylsilyl)-2-deoxy-α-L-threo-4-thiopentofuranosyl]thymine | 1017604-43-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 1-[4-O-acetoxy-5-O-acetyl-3-O-(tert-butyldimethylsilyl)-2-deoxy-α-L-threo-4-thiopentofuranosyl]thymine
• 英文别名: [(2S,3S,5R)-2-acetyloxy-3-[tert-butyl(dimethyl)silyl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)thiolan-2-yl]methyl acetate
• CAS: 1017604-43-1
• 化学式: C₂₀H₃₂N₂O₇SSi
• 分子量: 472.635
• InChiKey: HXNYZEQLWZNCDI-YRNRMSPPSA-N

物化性质

• 密度：
  1.23±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.69
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  137
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-[4-O-acetoxy-5-O-acetyl-3-O-(tert-butyldimethylsilyl)-2-deoxy-α-L-threo-4-thiopentofuranosyl]thymine 在 叠氮基三甲基硅烷 、 四氯化锡 作用下， 以 二氯甲烷 为溶剂， 反应 7.0h， 以69%的产率得到1-[5-O-acetyl-4-azido-3-O-(tert-butyldimethylsilyl)-2-deoxy-β-D-erythro-4-thiopentofuranosyl]thymine
  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
• 作为产物：
  描述：

  1-[3-O-(t-butyldimethylsilyl)-2,5-dideoxy-β-D-glycero-4-eno-4-thiofuranosyl]thymine 、 lead(IV) tetraacetate 在 sodium carbonate 作用下， 以 苯 为溶剂， 以56%的产率得到1-[4-O-acetoxy-5-O-acetyl-3-O-(tert-butyldimethylsilyl)-2-deoxy-α-L-threo-4-thiopentofuranosyl]thymine
  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