(E,2R,4S,5R)-1-<4-azidotetrahydro-5-<2-(O-phenylphosphono)vinyl>-2-furyl>thymine | 142802-36-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (E,2R,4S,5R)-1-<4-azidotetrahydro-5-<2-(O-phenylphosphono)vinyl>-2-furyl>thymine
• 英文别名: [(E)-2-[(2R,3S,5R)-3-azido-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)tetrahydrofuran-2-yl]vinyl]-phenoxy-phosphinic acid；[(E)-2-[(2R,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]ethenyl]-phenoxyphosphinic acid
• CAS: 142802-36-6
• 化学式: C₁₇H₁₈N₅O₆P
• 分子量: 419.334
• InChiKey: UKEWTKWMSKHTON-HKJFTIBCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  120
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (E,2R,4S,5R)-1-<4-azidotetrahydro-5-<2-(O-phenylphosphono)vinyl>-2-furyl>thymine 在 sodium hydroxide 、 phosphodiesterase 作用下， 以 水 为溶剂， 以79%的产率得到(E,2R,4S,5R)-1-<4-azidotetrahydro-5-<2-phosphonovinyl>-2-furyl>thymine
  参考文献：
  名称：

  3'-Azido-3',5'-dideoxythymidine-5'-methylphosphonic acid diphosphate: synthesis and HIV-1 reverse transcriptase inhibition.

  摘要：

  3'-Azido-3'-deoxythymidine-5'-phosphonate was synthesized by a five-step reaction sequence. The 5'-phosphonate was inactive against HIV-1 in MT4 cells. The absence of activity against HIV-1 was at least partially explained by demonstrating that the K(m) value for the 5-deoxy-5-methylphosphonic acid diphosphate analog with HIV-1 reverse transcriptase (RT) was 320-fold greater than the K(m) value for 3'-azido-3'-deoxythymidine-5-triphosphate (AZTTP), and the k(cat) value for the 5-deoxy-5-methylphosphonic acid diphosphate analog was one-seventh the value for AZTTP. These differences in kinetic constants were due to a change in the rate-determining step from dissociation of the RT chain-terminated template-primer complex to the catalytic step. Thus, substitution of a methylene group for the 5-oxygen atom of AZTTP resulted in an 1800-fold reduction in the rate constant for RT-catalyzed phosphodiester bond formation.

  DOI：

  10.1021/jm00095a014
• 作为产物：
  描述：

  diphenyl [(triphenylphosphoranylidene)methyl]phosphonate 在 sodium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 (E,2R,4S,5R)-1-<4-azidotetrahydro-5-<2-(O-phenylphosphono)vinyl>-2-furyl>thymine
  参考文献：
  名称：

  3'-Azido-3',5'-dideoxythymidine-5'-methylphosphonic acid diphosphate: synthesis and HIV-1 reverse transcriptase inhibition.

  摘要：

  3'-Azido-3'-deoxythymidine-5'-phosphonate was synthesized by a five-step reaction sequence. The 5'-phosphonate was inactive against HIV-1 in MT4 cells. The absence of activity against HIV-1 was at least partially explained by demonstrating that the K(m) value for the 5-deoxy-5-methylphosphonic acid diphosphate analog with HIV-1 reverse transcriptase (RT) was 320-fold greater than the K(m) value for 3'-azido-3'-deoxythymidine-5-triphosphate (AZTTP), and the k(cat) value for the 5-deoxy-5-methylphosphonic acid diphosphate analog was one-seventh the value for AZTTP. These differences in kinetic constants were due to a change in the rate-determining step from dissociation of the RT chain-terminated template-primer complex to the catalytic step. Thus, substitution of a methylene group for the 5-oxygen atom of AZTTP resulted in an 1800-fold reduction in the rate constant for RT-catalyzed phosphodiester bond formation.

  DOI：

  10.1021/jm00095a014

文献信息

• 3'-Azido-3',5'-dideoxythymidine-5'-methylphosphonic acid diphosphate: synthesis and HIV-1 reverse transcriptase inhibition.
  作者：G. A. Freeman、J. L. Rideout、W. H. Miller、J. E. Reardon

  DOI：10.1021/jm00095a014

  日期：1992.8

  3'-Azido-3'-deoxythymidine-5'-phosphonate was synthesized by a five-step reaction sequence. The 5'-phosphonate was inactive against HIV-1 in MT4 cells. The absence of activity against HIV-1 was at least partially explained by demonstrating that the K(m) value for the 5-deoxy-5-methylphosphonic acid diphosphate analog with HIV-1 reverse transcriptase (RT) was 320-fold greater than the K(m) value for 3'-azido-3'-deoxythymidine-5-triphosphate (AZTTP), and the k(cat) value for the 5-deoxy-5-methylphosphonic acid diphosphate analog was one-seventh the value for AZTTP. These differences in kinetic constants were due to a change in the rate-determining step from dissociation of the RT chain-terminated template-primer complex to the catalytic step. Thus, substitution of a methylene group for the 5-oxygen atom of AZTTP resulted in an 1800-fold reduction in the rate constant for RT-catalyzed phosphodiester bond formation.