1-[2-deoxy-2-iodo-3,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-4-thio-β-D-ribofuranosyl]thymine | 1017605-10-5

• 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-[2-deoxy-2-iodo-3,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-4-thio-β-D-ribofuranosyl]thymine
• 英文别名: 1-[(6aR,8R,9R,9aR)-9-iodo-2,2,4,4-tetra(propan-2-yl)-6a,8,9,9a-tetrahydro-6H-thieno[3,2-f][1,3,5,2,4]trioxadisilocin-8-yl]-5-methylpyrimidine-2,4-dione
• CAS: 1017605-10-5
• 化学式: C₂₂H₃₉IN₂O₅SSi₂
• 分子量: 626.704
• InChiKey: UUEYLTFGECQDNG-ANTGDGSKSA-N

物化性质

• 密度：
  1.35±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.22
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-[2-deoxy-2-iodo-3,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-4-thio-β-D-ribofuranosyl]thymine 在 三乙基硼 、 氧气 、 三正丁基氢锡 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 1.5h， 以100%的产率得到1-[2-deoxy-3,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-4-thio-β-D-ribofuranosyl]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：

  1,4-anhydro-2-deoxy-3,5-O-(1,1,3,3-tetraisopropyldisiloxan-1,3-diyl)-4-thio-D-erythro-pent-1-enitol 、 O,O-二(三甲基甲硅烷基)胸苷 在 N-碘代丁二酰亚胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 5.0h， 以75%的产率得到1-[2-deoxy-2-iodo-3,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-4-thio-β-D-ribofuranosyl]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