[(2S,5R)-5-(4-acetamido-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl 2-acetyloxybenzoate | 126430-21-5

• 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: [(2S,5R)-5-(4-acetamido-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl 2-acetyloxybenzoate
• CAS: 126430-21-5
• 化学式: C₂₀H₂₁N₃O₇
• 分子量: 415.403
• InChiKey: VBUPSZBUYBDGBU-KBXCAEBGSA-N

物化性质

• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  124
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  [(2S,5R)-5-(4-acetamido-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl 2-acetyloxybenzoate 在 苄基三甲基氢氧化铵 作用下， 以 甲醇 为溶剂， 以62%的产率得到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：

  [(2S,5R)-5-(4-acetamido-2-oxopyrimidin-1-yl)-2,5-dihydrofuran-2-yl]methyl 2-acetyloxybenzoate 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 以970 mg的产率得到[(2S,5R)-5-(4-acetamido-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl 2-acetyloxybenzoate
  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

• Verfahren zur Herstellung von 2',3'-dideoxycytidin
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0341704A2

  公开（公告）日：1989-11-15

  Die Erfindung betrifft ein Verfahren zur Herstellung von 2′,3′-Dideoxycytidin, dadurch gekennzeichnet, dass man a) die 4-Aminogruppe von Cytidin mit einer geeigneten Schutzgruppe schützt, b) das geschützte Cytidin zum entsprechenden Brom­acetatderivat bromacetyliert, c) das Bromatom und die Acetoxygruppe aus dem Brom­acetat reduktiv eliminiert um das 2′,3′-Didehydro­derivat zu erhalten, d) das 2′,3′-Didehydroderivat hydriert und e) aus dem so erhaltenen an der 4-Amino und 5′-Hydroxygruppe geschützten 2′,3′-Dideoxycytidin die Schutzgruppen entfernt, um 2′,3′-Dideoxycytidin zu erhalten; sowie neue in diesem Verfahren vorkommende Zwischenprodukte.

  本发明涉及一种制备 2′，3′-二脱氧胞苷的工艺，其特征在于 a) 用适当的保护基团保护胞苷的 4-氨基 b) 将被保护的胞苷溴乙酰化为相应的溴乙酸酯衍生物 c) 还原消除溴乙酸酯中的溴原子和乙酰氧基，得到 2′，3′-二脱氢衍生物、 d) 将 2′,3′-二脱氢衍生物氢化，并 e) 从这样得到的 2′,3′-二脱氧胞苷中除去 4-氨基和 5′-羟基上的保护基团，得到 2′,3′-二脱氧胞苷； 以及在这一过程中出现的新型中间产物。
• BELICA, PETER S.;HUANG, TAI-NANG;MANCHAND, PERSY S.;PARTRIDGE, JOHN J.;TA+
  作者：BELICA, PETER S.、HUANG, TAI-NANG、MANCHAND, PERSY S.、PARTRIDGE, JOHN J.、TA+

  DOI：——

  日期：——