methyl (2S)-2-[[[(3S,4R,5R)-3-fluoro-4-phenylmethoxycarbonyloxy-5-(phenylmethoxycarbonyloxymethyl)oxolan-2-yl]oxy-phenoxyphosphoryl]amino]-3-methylbutanoate | 1443987-30-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl (2S)-2-[[[(3S,4R,5R)-3-fluoro-4-phenylmethoxycarbonyloxy-5-(phenylmethoxycarbonyloxymethyl)oxolan-2-yl]oxy-phenoxyphosphoryl]amino]-3-methylbutanoate
• CAS: 1443987-30-1
• 化学式: C₃₃H₃₇FNO₁₂P
• 分子量: 689.628
• InChiKey: DHASFUKTMWUQGE-OEAQGWQBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  48
• 可旋转键数：
  20
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  154
• 氢给体数：
  1
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  methyl (2S)-2-[[[(3S,4R,5R)-3-fluoro-4-phenylmethoxycarbonyloxy-5-(phenylmethoxycarbonyloxymethyl)oxolan-2-yl]oxy-phenoxyphosphoryl]amino]-3-methylbutanoate 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 2-deoxy-2-fluoro-α-D-arabinofuranose (P_R)-1-O-phenyl-(methoxy-valinyl)phosphate 、 2-deoxy-2-fluoro-α-D-arabinofuranose (P_S)-1-O-phenyl-(methoxy-valinyl)phosphate
  参考文献：
  名称：

  Synthesis and biological evaluation of prodrugs of 2-fluoro-2-deoxyribose-1-phosphate and 2,2-difluoro-2-deoxyribose-1-phosphate

  摘要：

  We report in this Letter the synthesis of prodrugs of 2-fluoro-2-deoxyarabinose-1-phosphate and 2,2-difluoro-2-deoxyribose-1-phosphate. We demonstrate the difficulty of realising a phosphorylation step on the anomeric position of 2-deoxyribose, and we discover that introduction of fluorine atoms on the 2 position of 2-deoxyribose enables the phosphorylation step: in fact, the stability of the prodrugs increases with the degree of 2-fluorination. Stability studies of produgs of 2-fluoro-2-deoxyribose-1-phosphate and 2,2-difluoro-2-deoxyribose-1-phosphate in acidic and neutral conditions were conducted to confirm our observation. Biological evaluation of prodrugs of 2,2-difluoro-2-deoxyribose-1-phosphate for antiviral and cytotoxic activity is reported. (C) 2013 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2013.02.117
• 作为产物：
  描述：

  2-deoxy-2-fluoro-3,5-di-O-benzyloxycarbonyl-D-arabinofuranose 、 chlorophenylphosphoryl (P->N)-L-valine methyl ester 在 叔丁基氯化镁 作用下， 以 四氢呋喃 为溶剂， 反应 0.33h， 生成 methyl (2S)-2-[[[(3S,4R,5R)-3-fluoro-4-phenylmethoxycarbonyloxy-5-(phenylmethoxycarbonyloxymethyl)oxolan-2-yl]oxy-phenoxyphosphoryl]amino]-3-methylbutanoate
  参考文献：
  名称：

  Synthesis and biological evaluation of prodrugs of 2-fluoro-2-deoxyribose-1-phosphate and 2,2-difluoro-2-deoxyribose-1-phosphate

  摘要：

  We report in this Letter the synthesis of prodrugs of 2-fluoro-2-deoxyarabinose-1-phosphate and 2,2-difluoro-2-deoxyribose-1-phosphate. We demonstrate the difficulty of realising a phosphorylation step on the anomeric position of 2-deoxyribose, and we discover that introduction of fluorine atoms on the 2 position of 2-deoxyribose enables the phosphorylation step: in fact, the stability of the prodrugs increases with the degree of 2-fluorination. Stability studies of produgs of 2-fluoro-2-deoxyribose-1-phosphate and 2,2-difluoro-2-deoxyribose-1-phosphate in acidic and neutral conditions were conducted to confirm our observation. Biological evaluation of prodrugs of 2,2-difluoro-2-deoxyribose-1-phosphate for antiviral and cytotoxic activity is reported. (C) 2013 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2013.02.117

文献信息

• Synthesis and biological evaluation of prodrugs of 2-fluoro-2-deoxyribose-1-phosphate and 2,2-difluoro-2-deoxyribose-1-phosphate
  作者：Nadege Hamon、Maurizio Quintiliani、Jan Balzarini、Christopher McGuigan

  DOI：10.1016/j.bmcl.2013.02.117

  日期：2013.5

  We report in this Letter the synthesis of prodrugs of 2-fluoro-2-deoxyarabinose-1-phosphate and 2,2-difluoro-2-deoxyribose-1-phosphate. We demonstrate the difficulty of realising a phosphorylation step on the anomeric position of 2-deoxyribose, and we discover that introduction of fluorine atoms on the 2 position of 2-deoxyribose enables the phosphorylation step: in fact, the stability of the prodrugs increases with the degree of 2-fluorination. Stability studies of produgs of 2-fluoro-2-deoxyribose-1-phosphate and 2,2-difluoro-2-deoxyribose-1-phosphate in acidic and neutral conditions were conducted to confirm our observation. Biological evaluation of prodrugs of 2,2-difluoro-2-deoxyribose-1-phosphate for antiviral and cytotoxic activity is reported. (C) 2013 Published by Elsevier Ltd.