[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)tetrahydrofuran-2-yl]methyl (4-nitrophenyl)methyl phenyl phosphate | 879688-49-0

• 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: [(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)tetrahydrofuran-2-yl]methyl (4-nitrophenyl)methyl phenyl phosphate
• 英文别名: [(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl (4-nitrophenyl)methyl phenyl phosphate
• CAS: 879688-49-0
• 化学式: C₂₃H₂₃N₆O₉P
• 分子量: 558.444
• InChiKey: OIBDDFMBNJIDOT-DCGDVLQRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  39
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  164
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  [(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)tetrahydrofuran-2-yl]methyl (4-nitrophenyl)methyl phenyl phosphate 在 三乙胺 作用下， 以 水 、 乙腈 为溶剂， 以83%的产率得到[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)tetrahydrofuran-2-yl]methyl phenyl hydrogen phosphate
  参考文献：
  名称：

  Aryl nucleoside H-phosphonates. Part 15: Synthesis, properties and, anti-HIV activity of aryl nucleoside 5′-α-hydroxyphosphonates

  摘要：

  Aryl nucleoside 5'-H-phosphonates 4 bearing AZT or 2',3'-dideoxyuridine moieties were subjected to reaction with various aromatic aldehydes to produce nucleoside 5'-alpha-hydroxyphosphonate derivatives 2 as potential anti-HIV agents. Stability of the title compounds in cell culture media was investigated and three distinct decomposition pathways were identified. The anti-HIV activity of hydroxyphosplionates 2 correlates well with the type and extent of their chemical or enzymatic degradation in Culture medium (RPMI 1640 containing 10% FBS), suggesting that aryl nucleoside 5'-hydroxyphosphonates 2 act as depot forms of the parent antiviral nucleosides. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.10.048
• 作为产物：
  描述：

  3'-azido-3'-deoxythymidin-5'-yl H-phosphonate monoester 在 吡啶 、 2,6-二甲基吡啶 、 三乙胺 、 氯磷酸二苯酯 作用下， 以 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 1.08h， 生成 [(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)tetrahydrofuran-2-yl]methyl (4-nitrophenyl)methyl phenyl phosphate
  参考文献：
  名称：

  Aryl nucleoside H-phosphonates. Part 15: Synthesis, properties and, anti-HIV activity of aryl nucleoside 5′-α-hydroxyphosphonates

  摘要：

  Aryl nucleoside 5'-H-phosphonates 4 bearing AZT or 2',3'-dideoxyuridine moieties were subjected to reaction with various aromatic aldehydes to produce nucleoside 5'-alpha-hydroxyphosphonate derivatives 2 as potential anti-HIV agents. Stability of the title compounds in cell culture media was investigated and three distinct decomposition pathways were identified. The anti-HIV activity of hydroxyphosplionates 2 correlates well with the type and extent of their chemical or enzymatic degradation in Culture medium (RPMI 1640 containing 10% FBS), suggesting that aryl nucleoside 5'-hydroxyphosphonates 2 act as depot forms of the parent antiviral nucleosides. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.10.048

文献信息

• Studies on the decomposition pathways of diastereoisomeric mixtures of aryl nucleoside α-hydroxyphosphonates under hydrolytic conditions. Synthesis of α-hydroxyphosphonate monoesters
  作者：Agnieszka Szymańska-Michalak、Jacek Stawiński、Adam Kraszewski

  DOI：10.1039/b9nj00717b

  日期：——

  mixtures) bearing different aryl groups, both in the ester and the hydroxymethine fragment, were investigated under various hydrolytic conditions. We found that in aqueous basic media, the stability and decomposition pathways of these compounds were governed by the electronic features of the aryl group in the hydroxymethine moiety (hydroxyphosphonate ⇌ H-phosphonate diester + aldehyde equilibria) and

  在各种水解条件下，研究了酯和羟基次甲基片段中带有不同芳基 的核苷α-羟基膦酸酯1（非对映异构混合物）的分解途径。我们发现，在碱性水溶液中，这些化合物的稳定性和分解途径受羟基次甲基部分中芳基的电子特征支配（羟基膦酸酯 ⇌ H-膦酸酯二酯+醛平衡）和攻击亲核试剂（α-亲核试剂，例如 次碘酸盐或过氧化物阴离子）。在hydroxyphosphonates的水解速率中观察到的差异显著1与它们的直径： -acylated衍生物指向由相邻的羟基功能施加的分子内酸催化的重要性。基于这些发现，为其他方面难以访问的有效合成协议羟基膦酸酯已经开发出类型7的单酯。