N⁴-acetyl-5'-O-(tert-butyldimethylsilyl)-2',3'-dideoxycytidine | 141171-32-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: N⁴-acetyl-5'-O-(tert-butyldimethylsilyl)-2',3'-dideoxycytidine
• 英文别名: N-[1-[(2R,5S)-5-[[tert-butyl(dimethyl)silyl]oxymethyl]oxolan-2-yl]-2-oxopyrimidin-4-yl]acetamide
• CAS: 141171-32-6
• 化学式: C₁₇H₂₉N₃O₄Si
• 分子量: 367.52
• InChiKey: APGCNHUJPAESDD-DZGCQCFKSA-N

物化性质

• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  80.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N⁴-acetyl-5'-O-(tert-butyldimethylsilyl)-2',3'-dideoxycytidine 在 甲醇 、 四丁基氟化铵 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 8.5h， 生成 2,3-二脱氧胞啶
  参考文献：
  名称：

  Syntheses of the anti-AIDS drug 2',3'-dideoxycytidine from cytidine

  摘要：

  Two efficient syntheses of the anti-AIDS drug 2',3'-dideoxycytidine (3) from N4-acetylcytidine (4) are described. In one, silylation of the C-5' hydroxyl group of 4 with tert-butyldimethylsilyl chloride followed by treatment with 1',1'-(thiocarbonyl)diimidazole gave the cyclic thionocarbonate 7, which on reaction with 1,3-dimethyl-2-phenyl-1,3-diazaphospholidine gave the crystalline alkene 8. Hydrogenation of 8, followed by desilylation with tetrabutylammonium fluoride and hydrolysis, gave 3 in 27% overall yield from 4. In the other synthesis, 4 was converted into a regioisomeric mixture of bromo acetates 11 with 2-acetoxy-2-methylpropanoyl bromide. Reductive elimination of 11 with zinc-copper couple in acetic acid or electrochemically gave the crystalline alkene 15, whose stereostructure was established by a single-crystal X-ray analysis. Hydrogenation of 15, followed by hydrolysis, gave ddC (3). In a through process, which is suitable for large-scale work, this second synthesis gave 3 in over 40% overall yield from 4. The use of (S)-(-)-2-acetoxypropanoyl bromide, of 2-acetoxybenzoyl bromide, and of hydrogen bromide/acetic acid in the bromoacetylation of 4 is also described.

  DOI：

  10.1021/jo00038a042
• 作为产物：
  描述：

  N-乙酰基-5'-O-[(叔丁基)二甲基硅烷基]胞苷 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 24.08h， 生成 N⁴-acetyl-5'-O-(tert-butyldimethylsilyl)-2',3'-dideoxycytidine
  参考文献：
  名称：

  Syntheses of the anti-AIDS drug 2',3'-dideoxycytidine from cytidine

  摘要：

  Two efficient syntheses of the anti-AIDS drug 2',3'-dideoxycytidine (3) from N4-acetylcytidine (4) are described. In one, silylation of the C-5' hydroxyl group of 4 with tert-butyldimethylsilyl chloride followed by treatment with 1',1'-(thiocarbonyl)diimidazole gave the cyclic thionocarbonate 7, which on reaction with 1,3-dimethyl-2-phenyl-1,3-diazaphospholidine gave the crystalline alkene 8. Hydrogenation of 8, followed by desilylation with tetrabutylammonium fluoride and hydrolysis, gave 3 in 27% overall yield from 4. In the other synthesis, 4 was converted into a regioisomeric mixture of bromo acetates 11 with 2-acetoxy-2-methylpropanoyl bromide. Reductive elimination of 11 with zinc-copper couple in acetic acid or electrochemically gave the crystalline alkene 15, whose stereostructure was established by a single-crystal X-ray analysis. Hydrogenation of 15, followed by hydrolysis, gave ddC (3). In a through process, which is suitable for large-scale work, this second synthesis gave 3 in over 40% overall yield from 4. The use of (S)-(-)-2-acetoxypropanoyl bromide, of 2-acetoxybenzoyl bromide, and of hydrogen bromide/acetic acid in the bromoacetylation of 4 is also described.

  DOI：

  10.1021/jo00038a042

文献信息

• Syntheses of the anti-AIDS drug 2',3'-dideoxycytidine from cytidine
  作者：Percy S. Manchand、Peter S. Belica、Michael J. Holman、Tai Nang Huang、Hubert Maehr、Steve Y. K. Tam、Roxana T. Yang

  DOI：10.1021/jo00038a042

  日期：1992.6

  Two efficient syntheses of the anti-AIDS drug 2',3'-dideoxycytidine (3) from N4-acetylcytidine (4) are described. In one, silylation of the C-5' hydroxyl group of 4 with tert-butyldimethylsilyl chloride followed by treatment with 1',1'-(thiocarbonyl)diimidazole gave the cyclic thionocarbonate 7, which on reaction with 1,3-dimethyl-2-phenyl-1,3-diazaphospholidine gave the crystalline alkene 8. Hydrogenation of 8, followed by desilylation with tetrabutylammonium fluoride and hydrolysis, gave 3 in 27% overall yield from 4. In the other synthesis, 4 was converted into a regioisomeric mixture of bromo acetates 11 with 2-acetoxy-2-methylpropanoyl bromide. Reductive elimination of 11 with zinc-copper couple in acetic acid or electrochemically gave the crystalline alkene 15, whose stereostructure was established by a single-crystal X-ray analysis. Hydrogenation of 15, followed by hydrolysis, gave ddC (3). In a through process, which is suitable for large-scale work, this second synthesis gave 3 in over 40% overall yield from 4. The use of (S)-(-)-2-acetoxypropanoyl bromide, of 2-acetoxybenzoyl bromide, and of hydrogen bromide/acetic acid in the bromoacetylation of 4 is also described.