1-[(2R,3R,4R,5S)-N-tert-butyloxycarbonyl-3-tert-butyldimethylsilyloxy-4-difluoromethyl-5-(tert-butyldimethylsilyloxymethyl)pyrrolidin-2-yl]thymine | 852616-91-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 1-[(2R,3R,4R,5S)-N-tert-butyloxycarbonyl-3-tert-butyldimethylsilyloxy-4-difluoromethyl-5-(tert-butyldimethylsilyloxymethyl)pyrrolidin-2-yl]thymine
• 英文别名: tert-butyl (2S,3R,4R,5R)-4-[tert-butyl(dimethyl)silyl]oxy-2-[[tert-butyl(dimethyl)silyl]oxymethyl]-3-(difluoromethyl)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)pyrrolidine-1-carboxylate
• CAS: 852616-91-2
• 化学式: C₂₈H₅₁F₂N₃O₆Si₂
• 分子量: 619.897
• InChiKey: XLTKNJXWCLTQAC-GLHSZLCASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.26
• 重原子数：
  41
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  97.4
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-[(2R,3R,4R,5S)-N-tert-butyloxycarbonyl-3-tert-butyldimethylsilyloxy-4-difluoromethyl-5-(tert-butyldimethylsilyloxymethyl)pyrrolidin-2-yl]thymine 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 以74%的产率得到1-[(2R,3R,4R,5S)-N-tert-butyloxycarbonyl-3-hydroxy-4-difluoromethyl-5-(hydroxymethyl)pyrrolidin-2-yl]thymine
  参考文献：
  名称：

  Synthesis of 3‘-Deoxy-3‘-difluoromethyl Azanucleosides from trans-4-Hydroxy-l-proline

  摘要：

  Two strategies were tried to synthesize 3'-deoxy-3'-difluoromethyl azanucleosides. After the failure of the first route, the key intermediate 12 from trans-4-hydroxyproline 7 in 8 steps was stereoselectively prepared. The alcohol 12 was subjected to selective protection, oxidation, and difluoromethylenation to afford the fluorinated compound 18, whose hydrogenation was then systematically investigated. After a series of transformations of protecting groups, the resultant compounds 22 and 23 were oxidized to the desired lactams 24 and 25, which were successfully utilized to synthesize our target molecules, 3'-deoxy-3'-difluoromethyl azanucleosides 33, 34a, 34b, and 35.

  DOI：

  10.1021/jo050057+
• 作为产物：
  描述：

  L-羟基脯氨酸 在 ruthenium(IV) oxide 、 palladium dihydroxide 吡啶 、 咪唑 、 六甲基磷酰三胺 、 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 sodium periodate 、 四氧化锇 、 lithium aluminium tetrahydride 、 氯化亚砜 、 N,O-双三甲硅基乙酰胺 、 二苯基二硒醚 、 四丁基氟化铵 、 氨 、 氢气 、 三乙基硼氢化锂 、 戴斯-马丁氧化剂 、 氧化-4-甲基吗啉一水合物 、 三乙胺 、 锌 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醚 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 丙酮 、 甲苯 、 乙腈 为溶剂， -78.0~20.0 ℃ 、10.13 MPa 条件下， 反应 71.0h， 生成 1-[(2R,3R,4R,5S)-N-tert-butyloxycarbonyl-3-tert-butyldimethylsilyloxy-4-difluoromethyl-5-(tert-butyldimethylsilyloxymethyl)pyrrolidin-2-yl]thymine
  参考文献：
  名称：

  Synthesis of 3‘-Deoxy-3‘-difluoromethyl Azanucleosides from trans-4-Hydroxy-l-proline

  摘要：

  Two strategies were tried to synthesize 3'-deoxy-3'-difluoromethyl azanucleosides. After the failure of the first route, the key intermediate 12 from trans-4-hydroxyproline 7 in 8 steps was stereoselectively prepared. The alcohol 12 was subjected to selective protection, oxidation, and difluoromethylenation to afford the fluorinated compound 18, whose hydrogenation was then systematically investigated. After a series of transformations of protecting groups, the resultant compounds 22 and 23 were oxidized to the desired lactams 24 and 25, which were successfully utilized to synthesize our target molecules, 3'-deoxy-3'-difluoromethyl azanucleosides 33, 34a, 34b, and 35.

  DOI：

  10.1021/jo050057+

文献信息

• Synthesis of 3‘-Deoxy-3‘-difluoromethyl Azanucleosides from <i>trans</i>-4-Hydroxy-<scp>l</scp>-proline
  作者：Xiao-Long Qiu、Feng-Ling Qing

  DOI：10.1021/jo050057+

  日期：2005.5.1

  Two strategies were tried to synthesize 3'-deoxy-3'-difluoromethyl azanucleosides. After the failure of the first route, the key intermediate 12 from trans-4-hydroxyproline 7 in 8 steps was stereoselectively prepared. The alcohol 12 was subjected to selective protection, oxidation, and difluoromethylenation to afford the fluorinated compound 18, whose hydrogenation was then systematically investigated. After a series of transformations of protecting groups, the resultant compounds 22 and 23 were oxidized to the desired lactams 24 and 25, which were successfully utilized to synthesize our target molecules, 3'-deoxy-3'-difluoromethyl azanucleosides 33, 34a, 34b, and 35.