tert-butyl (2S,5S)-2-(6-chloropurin-9-yl)-3,3-difluoro-5-(hydroxymethyl)pyrrolidine-1-carboxylate | 1415008-13-7

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: tert-butyl (2S,5S)-2-(6-chloropurin-9-yl)-3,3-difluoro-5-(hydroxymethyl)pyrrolidine-1-carboxylate
• CAS: 1415008-13-7
• 化学式: C₁₅H₁₈ClF₂N₅O₃
• 分子量: 389.789
• InChiKey: JQXKUBUMPFEVRL-UFBFGSQYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  93.4
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tert-butyl (2S,5S)-2-(6-chloropurin-9-yl)-3,3-difluoro-5-(hydroxymethyl)pyrrolidine-1-carboxylate 在 氨 作用下， 以 甲醇 为溶剂， 以72%的产率得到tert-butyl (2S,5S)-2-(6-aminopurin-9-yl)-3,3-difluoro-5-(hydroxymethyl)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  Synthesis, evaluation of anti-HIV-1 and anti-HCV activity of novel 2′,3′-dideoxy-2′,2′-difluoro-4′-azanucleosides

  摘要：

  A series of 2',3'-dideoxy-2',2'-difluoro-4'-azanucleosides of both pyrimidine and purine nucleobases were synthesized in an efficient manner starting from commercially available L-pyroglutamic acid via glycosylation of difluorinated pyrrolidine derivative 15. Several 4'-azanucleosides were prepared as a separable mixture of alpha- and beta-anomers. The 6-chloropurine analogue was obtained as a mixture of N-7 and N-9 regioisomers and their structures were identified based on NOESY and HMBC spectral data. Among the 4'-azanucleosides tested as HIV-1 inhibitors in primary human lymphocytes, four compounds showed modest activity and the 5-fluorouracil analogue (18d) was found to be the most active compound (EC50 = 36.9 mu M) in this series. None of the compounds synthesized in this study demonstrated anti-HCV activity. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.09.026
• 作为产物：
  描述：

  在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以82%的产率得到tert-butyl (2S,5S)-2-(6-chloropurin-9-yl)-3,3-difluoro-5-(hydroxymethyl)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  Synthesis, evaluation of anti-HIV-1 and anti-HCV activity of novel 2′,3′-dideoxy-2′,2′-difluoro-4′-azanucleosides

  摘要：

  A series of 2',3'-dideoxy-2',2'-difluoro-4'-azanucleosides of both pyrimidine and purine nucleobases were synthesized in an efficient manner starting from commercially available L-pyroglutamic acid via glycosylation of difluorinated pyrrolidine derivative 15. Several 4'-azanucleosides were prepared as a separable mixture of alpha- and beta-anomers. The 6-chloropurine analogue was obtained as a mixture of N-7 and N-9 regioisomers and their structures were identified based on NOESY and HMBC spectral data. Among the 4'-azanucleosides tested as HIV-1 inhibitors in primary human lymphocytes, four compounds showed modest activity and the 5-fluorouracil analogue (18d) was found to be the most active compound (EC50 = 36.9 mu M) in this series. None of the compounds synthesized in this study demonstrated anti-HCV activity. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.09.026

文献信息

• Synthesis, evaluation of anti-HIV-1 and anti-HCV activity of novel 2′,3′-dideoxy-2′,2′-difluoro-4′-azanucleosides
  作者：Saúl Martínez-Montero、Susana Fernández、Yogesh S. Sanghvi、Emmanuel A. Theodorakis、Mervi A. Detorio、Tamara R. Mcbrayer、Tony Whitaker、Raymond F. Schinazi、Vicente Gotor、Miguel Ferrero

  DOI：10.1016/j.bmc.2012.09.026

  日期：2012.12

  A series of 2',3'-dideoxy-2',2'-difluoro-4'-azanucleosides of both pyrimidine and purine nucleobases were synthesized in an efficient manner starting from commercially available L-pyroglutamic acid via glycosylation of difluorinated pyrrolidine derivative 15. Several 4'-azanucleosides were prepared as a separable mixture of alpha- and beta-anomers. The 6-chloropurine analogue was obtained as a mixture of N-7 and N-9 regioisomers and their structures were identified based on NOESY and HMBC spectral data. Among the 4'-azanucleosides tested as HIV-1 inhibitors in primary human lymphocytes, four compounds showed modest activity and the 5-fluorouracil analogue (18d) was found to be the most active compound (EC50 = 36.9 mu M) in this series. None of the compounds synthesized in this study demonstrated anti-HCV activity. (C) 2012 Elsevier Ltd. All rights reserved.