1-((2R,4R,5R)-4,5-Bis-hydroxymethyl-[1,3]oxathiolan-2-yl)-5-methyl-1H-pyrimidine-2,4-dione

• 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-((2R,4R,5R)-4,5-Bis-hydroxymethyl-[1,3]oxathiolan-2-yl)-5-methyl-1H-pyrimidine-2,4-dione
• 英文别名: 1-[(2R,4R,5R)-4,5-bis(hydroxymethyl)-1,3-oxathiolan-2-yl]-5-methyl-pyrimidine-2,4-dione；1-[(2R,4R,5R)-4,5-bis(hydroxymethyl)-1,3-oxathiolan-2-yl]-5-methylpyrimidine-2,4-dione
• 化学式: C₁₀H₁₄N₂O₅S
• 分子量: 274.298
• InChiKey: UJLCWVQUGYBYBA-BRDIYROLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  18
• 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：
  124
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  胸腺嘧啶 在 ammonium sulfate 、 三甲基氯硅烷 、 三氟甲磺酸三甲基硅酯 、 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 1-((2R,4R,5R)-4,5-Bis-hydroxymethyl-[1,3]oxathiolan-2-yl)-5-methyl-1H-pyrimidine-2,4-dione
  参考文献：
  名称：

  Synthesis of [4,5-Bis(hydroxymethyl)-1,3-oxathiolan-2-yl]nucleosides as Potential Inhibitors of HIV via Stereospecific Base-Induced Rearrangement of a 2,3-Epoxy Thioacetate¹

  摘要：

  The synthesis of [4,5-bis(hydroxymethyl)-1,3-oxathiolan-2-yl]nucleosides is described. 2,3-Epoxy alcohol 10 was converted in one pot into thioacetate 11. Treatment of 11 under mild alkaline conditions gave thiirane 12 with inversion of configuration at C-2. We also found that thioacetate 11 rearranges into thiirane 14 under mild acidic conditions. This rearrangement reaction was shown by independent synthesis to proceed with net retention of configuration at C-2. We have proposed a tentative mechanism which may explain the results obtained. Opening of thiiranes 12; and 14 followed by deprotection gave (2R,3R)-2-thiothreitol (23) and (2S,3R)-2-thioerythritol (25), respectively. Regioselective silylation of the primary hydroxyl groups of 23 followed by treatment with trimethyl orthoformate gave 2-methoxy-1,3-oxathiolanes 26 and 27. Condensation with silylated baser followed by deprotection and separation of the anomers gave the oxathiolanyl-nucleosides. Compounds 29-31, 34, and 35 were found to be inactive when tested for inhibition of HIV-1 activity in vitro.

  DOI：

  10.1021/jo960009c

文献信息

• Synthesis of [4,5-Bis(hydroxymethyl)-1,3-oxathiolan-2-yl]nucleosides as Potential Inhibitors of HIV via Stereospecific Base-Induced Rearrangement of a 2,3-Epoxy Thioacetate¹
  作者：Jonas Brånalt、Ingemar Kvarnström、Björn Classon、Bertil Samuelsson

  DOI：10.1021/jo960009c

  日期：1996.1.1

  The synthesis of [4,5-bis(hydroxymethyl)-1,3-oxathiolan-2-yl]nucleosides is described. 2,3-Epoxy alcohol 10 was converted in one pot into thioacetate 11. Treatment of 11 under mild alkaline conditions gave thiirane 12 with inversion of configuration at C-2. We also found that thioacetate 11 rearranges into thiirane 14 under mild acidic conditions. This rearrangement reaction was shown by independent synthesis to proceed with net retention of configuration at C-2. We have proposed a tentative mechanism which may explain the results obtained. Opening of thiiranes 12; and 14 followed by deprotection gave (2R,3R)-2-thiothreitol (23) and (2S,3R)-2-thioerythritol (25), respectively. Regioselective silylation of the primary hydroxyl groups of 23 followed by treatment with trimethyl orthoformate gave 2-methoxy-1,3-oxathiolanes 26 and 27. Condensation with silylated baser followed by deprotection and separation of the anomers gave the oxathiolanyl-nucleosides. Compounds 29-31, 34, and 35 were found to be inactive when tested for inhibition of HIV-1 activity in vitro.