(+/-)-2',3'-didehydro-3'-deoxy-4'-hydroxymethyl-4'-thiothymidine | 923261-59-0

• 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: (+/-)-2',3'-didehydro-3'-deoxy-4'-hydroxymethyl-4'-thiothymidine
• 英文别名: 1-[5,5-bis(hydroxymethyl)-2H-thiophen-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 923261-59-0
• 化学式: C₁₁H₁₄N₂O₄S
• 分子量: 270.309
• InChiKey: FEQUSEZNELTYSA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  115
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (+/-)-2',3'-didehydro-3'-deoxy-4'-hydroxymethyl-4'-thiothymidine 、 乙酸酐 在 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 以115 g的产率得到
  参考文献：
  名称：

  Synthesis and Anti-Human Immunodeficiency Virus Activity of 4‘-Branched (±)-4‘-Thiostavudines

  摘要：

  Motivated by our recent finding that 4'-ethynylstavudine (4) is a promising anti-human immunodeficiency virus type 1 (HIV-1) agent, we synthesized its 4'-thio analogue, as well as other 4'-thiostavudines having a carbon substituent at the 4'-position, as racemates in this study. Methyl 3-oxo-tetrahydrothiophen-2-carboxylate (5) was used as a starting material to construct the requisite 4-thiofuranoid glycal (13). Introduction of a thymine base was carried out by an electrophilic addition reaction to 13 using N-iodosuccinimide (NIS) and bis(trimethylsilyl)thymine. The desired beta-anomer (16 beta) obtained as a major product in this reaction underwent ready elimination with activated Zn to give the 4'-carbomethoxy derivative (18). By using 18 as a common intermediate, 4'-carbon-substituted (CH2OH, CO2Me, CONH2, CHCH2, CN, and CCH) 4'-thiostavudines were prepared. Among these six compounds, 4'-cyano (28) and 4'-ethynyl (29) analogues were found to show inhibitory activity against HIV-1 with ED50 values of 7.6 and 0.74 mu M, respectively. The activity of 29 was comparable to that of stavudine, but 29 was not as active as 4. Optical resolution of 29 was briefly examined.

  DOI：

  10.1021/jm060980j
• 作为产物：
  描述：

  在 水 、 二甲胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 29.0h， 以100%的产率得到(+/-)-2',3'-didehydro-3'-deoxy-4'-hydroxymethyl-4'-thiothymidine
  参考文献：
  名称：

  2'-Deoxy-4'-C-hydroxymethyl-4'-thioribonucleosides 及其 2',3'-Dideoxy 和 2',3'-Didehydro-2',3'-dideoxy 类似物的合成

  摘要：

  - (±)-2'-Deoxy-4'-C-hydroxymethyl-4'-thioribonucleosides (1) 及其 2', 3'-dideoxy- (2) 和 2', 3'-didehydro-2', 3 '-二脱氧- (3) 类似物已从氢噻吩衍生物 2,2-双(苄氧基甲基)-3-苄氧基四氢噻吩 (4)、2,2-双-(乙酰氧基甲基)四氢噻吩 (5) 和 2,2-双(乙酰氧基甲基）-2,5-二氢噻吩（6）。化合物 1 的制备通过相应的亚砜 9 进行 N-糖基化，通过 m-CPBA 氧化衍生自 4，用三甲基甲硅烷基化的嘧啶和三甲基甲硅烷基三氟甲磺酸酯（Kita-O'Niel-Matsuda 的方法；改进的 Pummerer 重排）。另一方面，化合物 2 和 3 是通过相应的 4' 的 N-糖基化获得的。

  DOI：

  10.3987/com-08-s(n)100