1-methyl-5-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)uracil | 110419-25-5

• 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: 1-methyl-5-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)uracil
• 英文别名: 5-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-1-methyluracil；5-[(2S,3S,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1-methylpyrimidine-2,4-dione
• CAS: 110419-25-5
• 化学式: C₁₀H₁₃FN₂O₅
• 分子量: 260.222
• InChiKey: BBEYIFXNCKMITQ-CWKFCGSDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.6
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  99.1
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-methyl-5-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)uracil 在 吡啶 、 CrO₃*pyridine*acetic anhydride 作用下， 以 二氯甲烷 为溶剂， 反应 73.0h， 生成 5-((2S,3R,5R)-3-Fluoro-4-oxo-5-trityloxymethyl-tetrahydro-furan-2-yl)-1-methyl-1H-pyrimidine-2,4-dione
  参考文献：
  名称：

  Nucleosides. 153. Synthesis of 1-methyl-5-(3-azido-2,3-dideoxy-.beta.-D-erythro-pentofuranosyl)uracil and 1-methyl-5-(3-azido-2,3-dideoxy-2-fluoro-.beta.-D-arabinofuranosyl)uracil. The C-nucleoside isostere of 3'-azido-3'-deoxythymidine and its 2'-"up"-fluoro analog

  摘要：

  1-Methyl-5-(3-azido-2,3-dideoxy-beta-D-erythro-pentofuranosyl)uracil (C-AZT), a C-nucleoside isostere of the potent anti-AIDS nucleoside 3'-azido-3'-deoxythymidine (AZT), was synthesized. 1-Methyl-2'-deoxy-5'-O-tritylpseudouridine (2a) was oxidized with CrO3/pyridine/Ac2O complex to 1-methyl-5-(5-O-trityl-beta-D-glycero-pentofuranos-3-ulosyl) uracil (12a), which was selectively reduced to 1-methyl-5-(5-O-trityl-beta-D-threo-pentofuranosyl)uracil (13a). Mesylation of 13a to 14a followed by nucleophilic displacement of the mesyloxy group with azide afforded 3'-azido-2',3'-dideoxy-5'-O-trityl-1-methylpseudoridine (15a), which was detritylated to C-AZT. In a similar manner, 1-methyl-5-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)uracil (C-FMAU, a potent antiherpetic nucleoside) was converted into the 3'-azido analogue (3'-azido-C-FMAU). Both C-AZT and 3'-azido-C-FMAU, however, did not exhibit any significant inhibitory activity against HIV in H9 cells.

  DOI：

  10.1021/jm00169a030
• 作为产物：
  描述：

  3'-O-acetyl-2'-O-triflyl-4,5'-anhydro-1-methyl-ψ-uridine 在 Dowex 50 (H⁺) 、 三(二甲氨基)锍二氟三甲基硅酸 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 5.5h， 生成 1-methyl-5-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)uracil
  参考文献：
  名称：

  Nucleosides. 146. 1-Methyl-5-(2-deoxy-2-fluoro-.beta.-D-arabinofuranosyl)uracil, the C-nucleoside isostere of the potent antiviral agent, 1-(2-deoxy-2-fluoro-.beta.-D-arabinofuranosyl)thymine (FMAU). Studies directed toward the synthesis of 2'-deoxy-2'-substituted arabino nucleosides. 6

  摘要：

  The synthesis of 5-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-1-methyluracil (1, C-FMAU), an isostere of the potent antiviral and antitumor nucleoside 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)thymine (2'-fluoro-5-methyl-ara-U or FMAU), was achieved. Pseudouridine (2) was converted into 4,5'-anhydro-3'-O-acetyl-2'-O-triflylpseudouridine (4), which was treated with tris(dimethylamino)sulfur (1+) difluorotrimethylsilicate (TASF) to give 4,5'-anhydro-5-(3-O-acetyl-2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-1- methyluracil (5b) in 40% yield. Acid hydrolysis of the 4,5'-anhydro linkage of 5b with Dowex 50 (H+) afforded C-FMAU. The inhibitory activity of C-FMAU against HSV-1 and HSV-2 was about 10-fold less than that of FMAU in tissue culture. This compound, however, did not show significant activity in mice inoculated with HSV-1 or HSV-2.

  DOI：

  10.1021/jm00395a023

文献信息

• SOCHACKA, ELZBIETA;NAWROT, BARBARA;PANKIEWICZ, KRZYSZTOF W.;WATANABE, KYO+, J. MED. CHEM., 33,(1990) N, C. 1995-1999
  作者：SOCHACKA, ELZBIETA、NAWROT, BARBARA、PANKIEWICZ, KRZYSZTOF W.、WATANABE, KYO+

  DOI：——

  日期：——
• PANKIEWICZ, KRZYSZTOF W.;NAWROT, BARBARA;SOCHACKA, ELZBIETA;WATANABE, KYO+, 7TH SYMP. CHEM. NUCL. ACID COMPON., BECHYNE CASTLE, AUG. 30TH - SEPT. 5TH+
  作者：PANKIEWICZ, KRZYSZTOF W.、NAWROT, BARBARA、SOCHACKA, ELZBIETA、WATANABE, KYO+

  DOI：——

  日期：——
• Nucleosides. 146. 1-Methyl-5-(2-deoxy-2-fluoro-.beta.-D-arabinofuranosyl)uracil, the C-nucleoside isostere of the potent antiviral agent, 1-(2-deoxy-2-fluoro-.beta.-D-arabinofuranosyl)thymine (FMAU). Studies directed toward the synthesis of 2'-deoxy-2'-substituted arabino nucleosides. 6
  作者：Krzysztof W. Pankiewicz、Barbara Nawrot、Hakan Gadler、Pichard W. Price、Kyoichi A. Watanabe

  DOI：10.1021/jm00395a023

  日期：1987.12

  The synthesis of 5-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-1-methyluracil (1, C-FMAU), an isostere of the potent antiviral and antitumor nucleoside 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)thymine (2'-fluoro-5-methyl-ara-U or FMAU), was achieved. Pseudouridine (2) was converted into 4,5'-anhydro-3'-O-acetyl-2'-O-triflylpseudouridine (4), which was treated with tris(dimethylamino)sulfur (1+) difluorotrimethylsilicate (TASF) to give 4,5'-anhydro-5-(3-O-acetyl-2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-1- methyluracil (5b) in 40% yield. Acid hydrolysis of the 4,5'-anhydro linkage of 5b with Dowex 50 (H+) afforded C-FMAU. The inhibitory activity of C-FMAU against HSV-1 and HSV-2 was about 10-fold less than that of FMAU in tissue culture. This compound, however, did not show significant activity in mice inoculated with HSV-1 or HSV-2.
• Nucleosides. 153. Synthesis of 1-methyl-5-(3-azido-2,3-dideoxy-.beta.-D-erythro-pentofuranosyl)uracil and 1-methyl-5-(3-azido-2,3-dideoxy-2-fluoro-.beta.-D-arabinofuranosyl)uracil. The C-nucleoside isostere of 3'-azido-3'-deoxythymidine and its 2'-"up"-fluoro analog
  作者：Elzbieta Sochacka、Barbara Nawrot、Krzysztof W. Pankiewicz、Kyoichi A. Watanabe

  DOI：10.1021/jm00169a030

  日期：1990.7

  1-Methyl-5-(3-azido-2,3-dideoxy-beta-D-erythro-pentofuranosyl)uracil (C-AZT), a C-nucleoside isostere of the potent anti-AIDS nucleoside 3'-azido-3'-deoxythymidine (AZT), was synthesized. 1-Methyl-2'-deoxy-5'-O-tritylpseudouridine (2a) was oxidized with CrO3/pyridine/Ac2O complex to 1-methyl-5-(5-O-trityl-beta-D-glycero-pentofuranos-3-ulosyl) uracil (12a), which was selectively reduced to 1-methyl-5-(5-O-trityl-beta-D-threo-pentofuranosyl)uracil (13a). Mesylation of 13a to 14a followed by nucleophilic displacement of the mesyloxy group with azide afforded 3'-azido-2',3'-dideoxy-5'-O-trityl-1-methylpseudoridine (15a), which was detritylated to C-AZT. In a similar manner, 1-methyl-5-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)uracil (C-FMAU, a potent antiherpetic nucleoside) was converted into the 3'-azido analogue (3'-azido-C-FMAU). Both C-AZT and 3'-azido-C-FMAU, however, did not exhibit any significant inhibitory activity against HIV in H9 cells.