4-amino-1-[(2S,5R)-5-[[tert-butyl(diphenyl)silyl]oxymethyl]-2,5-dihydrofuran-2-yl]-5-fluoropyrimidin-2-one | 189818-66-4

• 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: 4-amino-1-[(2S,5R)-5-[[tert-butyl(diphenyl)silyl]oxymethyl]-2,5-dihydrofuran-2-yl]-5-fluoropyrimidin-2-one
• CAS: 189818-66-4
• 化学式: C₂₅H₂₈FN₃O₃Si
• 分子量: 465.6
• InChiKey: PQAORAROPACSKH-GCJKJVERSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.99
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  77.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-amino-1-[(2S,5R)-5-[[tert-butyl(diphenyl)silyl]oxymethyl]-2,5-dihydrofuran-2-yl]-5-fluoropyrimidin-2-one 在 triethylamine trihydrofluoride 作用下， 以 四氢呋喃 为溶剂， 反应 20.0h， 以94%的产率得到艾夫他滨
  参考文献：
  名称：

  Stereoselective Syntheses of β-l-FD4C and β-l-FddC

  摘要：

  Stereocontrolled syntheses of two potent antiviral agents, beta-L-FD4C and beta-L-FddC, were accomplished both in 10-step sequences, with an overall yield of 27% and 25%, respectively. It is worthwhile to mention that the introduction of a phenylseleno moiety to the C-2 alpha position of the lactone 4 can now be performed in a stereocontrolled fashion, providing the key intermediate 5 alpha in 75% yield.

  DOI：

  10.1021/jo970177k
• 作为产物：
  描述：

  (R)-5-{[(tert-butyldiphenylsilyl)oxy]methyl}dihydrofuran-2(3H)-one 在 吡啶 、 4-二甲氨基吡啶 、 三甲基氯硅烷 、 三氟甲磺酸三甲基硅酯 、 双氧水 、 二异丁基氢化铝 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 1,2-二氯乙烷 、 甲苯 为溶剂， 反应 48.0h， 生成 4-amino-1-[(2S,5R)-5-[[tert-butyl(diphenyl)silyl]oxymethyl]-2,5-dihydrofuran-2-yl]-5-fluoropyrimidin-2-one
  参考文献：
  名称：

  Stereoselective Syntheses of β-l-FD4C and β-l-FddC

  摘要：

  Stereocontrolled syntheses of two potent antiviral agents, beta-L-FD4C and beta-L-FddC, were accomplished both in 10-step sequences, with an overall yield of 27% and 25%, respectively. It is worthwhile to mention that the introduction of a phenylseleno moiety to the C-2 alpha position of the lactone 4 can now be performed in a stereocontrolled fashion, providing the key intermediate 5 alpha in 75% yield.

  DOI：

  10.1021/jo970177k

文献信息

• Bis-S-acyl-2-thioethyl (sate)-bearing monophosphate prodrug of β-L-FD4C as potent anti-HBV agent
  作者：Xiuyan Li、Ellen Carmichael、Ming Feng、Ivan King、Terrence W. Doyle、Shu-Hui Chen

  DOI：10.1016/s0960-894x(97)10178-0

  日期：1998.1

  The S-acyl-2-thioethyl (SATE)-bearing 5'-monophosphate prodrug of beta-L-FD4C (8) was synthesized and evaluated for its activity against HBV in the 2.2.15 cell line. This pronucleotide (8) exhibited an excellent inhibitory effect against HBV with an EC50 value that is more than eight fold lower than that of the parent nucleoside (4) under some assay conditions. It is also important to note that pronucleotide (8) was capable of inhibiting HBV replication by 90%; whereas its parent, beta-L-FD4C (4), could only inhibit virus replication no greater than 70% in the same assay. When evaluated in the standard cytotoxicity assay in CEM cell line, pronucleotide (8) exhibited an IC50 value of 52 mu M, which was four times less toxic than parent beta-L-FD4C (4) (IC50 = 13 mu M). (C) 1997 Elsevier Science Ltd. All rights reserved.
• J. Org. Chem. 1997, 62, 3449-3452
  作者：

  DOI：——

  日期：——
• Stereoselective Syntheses of β-<scp>l</scp>-FD4C and β-<scp>l</scp>-FddC
  作者：Shu-Hui Chen、Xiuyan Li、Jun Li、Chuansheng Niu、Ellen Carmichael、Terrence W. Doyle

  DOI：10.1021/jo970177k

  日期：1997.5.1

  Stereocontrolled syntheses of two potent antiviral agents, beta-L-FD4C and beta-L-FddC, were accomplished both in 10-step sequences, with an overall yield of 27% and 25%, respectively. It is worthwhile to mention that the introduction of a phenylseleno moiety to the C-2 alpha position of the lactone 4 can now be performed in a stereocontrolled fashion, providing the key intermediate 5 alpha in 75% yield.