(-)-trans-(5S,6S)-5-bromo-6-hydroxy-5,6-dihydro-2',3'-didehydro-3'-deoxythymidine

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: (-)-trans-(5S,6S)-5-bromo-6-hydroxy-5,6-dihydro-2',3'-didehydro-3'-deoxythymidine
• 英文别名: (5S,6S)-5-bromo-6-hydroxy-1-[(2R,5S)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]-5-methyl-hexahydropyrimidine-2,4-dione；(5S,6S)-5-bromo-6-hydroxy-1-[(2R,5S)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]-5-methyl-1,3-diazinane-2,4-dione
• 化学式: C₁₀H₁₃BrN₂O₅
• 分子量: 321.128
• InChiKey: PMZVXBDNXMLJJK-CVUIIHQFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  99.1
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  司他夫定 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 水 为溶剂， 反应 0.33h， 以43%的产率得到(+)-trans-(5R,6R)-5-bromo-6-hydroxy-5,6-dihydro-2',3'-didehydro-3'-deoxythymidine
  参考文献：
  名称：

  Synthesis,In VitroBiological Stability, and Anti-HIV Activity of 5-Halo (or Methoxy)-6-Alkoxy (Azido or Hydroxy)-5,6-Dihydro-2′,3′-Didehydro-3′-Deoxythymidine Diastereomers as Potential Prodrugs of 2′,3′-Didehydro-3′-deoxythymidine (D4T)

  摘要：

  A new class of 5-halo (or methoxy)-6-alkoxy (azido or hydroxy)-5,6-dihydro-2',3'-didehydro-3'-deoxythymidines (4-17) were investigated as potential anti-AIDS drugs. These 5,6-dihydro derivatives, which are also potential prodrugs of 2',3'-didehydro-3'-deoxythymidine (D4T) were designed to have properties which would enhance their duration of action, lipophilicity and cephalic delivery to the central nervous system. The 5,6-dihydro derivatives of D4T (4-15), which differ in configuration at the C-5 and C-6 positions, were synthesized by the regiospecific addition of XR (X = Br, Cl, I; R = OMe, OEt, N-3, OH) to the 5,6-olefinic bond of D4T. These 5,6-disubstituted-5,6-dihydro analogs of D4T are more lipophilic (P = 0.70 - 4.0 range) than D4T (P = 0.12) and are stable to E, coli thymidine phosphorylase. Regeneration of the 5,6-olefinic bond to give D4T, upon incubation of the 5-bromo- and 5-iodo-6-methoxy-5,6-dihydro derivatives (6, 7, 10, 11) with glutathione or a mouse liver soluble enzyme fraction, was extensive (50-95%). The most potent anti-HIV-1 agents, 5-iodo-6-methoxy (10, 11), 5-bromo-6-azido (14, 15) and 5-methoxy-6-hydroxy (16, 17) derivatives of D4T, exhibited anti-HIV activities comparable to D4T.

  DOI：

  10.1080/07328319608002384

文献信息

• Synthesis,<i>In Vitro</i>Biological Stability, and Anti-HIV Activity of 5-Halo (or Methoxy)-6-Alkoxy (Azido or Hydroxy)-5,6-Dihydro-2′,3′-Didehydro-3′-Deoxythymidine Diastereomers as Potential Prodrugs of 2′,3′-Didehydro-3′-deoxythymidine (D4T)
  作者：Rakesh Kumar、Lili Wang、Leonard I. Wiebe、Edward E. Knaus

  DOI：10.1080/07328319608002384

  日期：1996.1

  A new class of 5-halo (or methoxy)-6-alkoxy (azido or hydroxy)-5,6-dihydro-2',3'-didehydro-3'-deoxythymidines (4-17) were investigated as potential anti-AIDS drugs. These 5,6-dihydro derivatives, which are also potential prodrugs of 2',3'-didehydro-3'-deoxythymidine (D4T) were designed to have properties which would enhance their duration of action, lipophilicity and cephalic delivery to the central nervous system. The 5,6-dihydro derivatives of D4T (4-15), which differ in configuration at the C-5 and C-6 positions, were synthesized by the regiospecific addition of XR (X = Br, Cl, I; R = OMe, OEt, N-3, OH) to the 5,6-olefinic bond of D4T. These 5,6-disubstituted-5,6-dihydro analogs of D4T are more lipophilic (P = 0.70 - 4.0 range) than D4T (P = 0.12) and are stable to E, coli thymidine phosphorylase. Regeneration of the 5,6-olefinic bond to give D4T, upon incubation of the 5-bromo- and 5-iodo-6-methoxy-5,6-dihydro derivatives (6, 7, 10, 11) with glutathione or a mouse liver soluble enzyme fraction, was extensive (50-95%). The most potent anti-HIV-1 agents, 5-iodo-6-methoxy (10, 11), 5-bromo-6-azido (14, 15) and 5-methoxy-6-hydroxy (16, 17) derivatives of D4T, exhibited anti-HIV activities comparable to D4T.