β-cyanoethyl-3'-azido-3'-deoxy-5'-thymidinyl N⁶,O^2'-dibenzoyl-3'-deoxy-5'-adenosinyl phosphate

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷酸
• 英文名称: β-cyanoethyl-3'-azido-3'-deoxy-5'-thymidinyl N⁶,O^2'-dibenzoyl-3'-deoxy-5'-adenosinyl phosphate
• 英文别名: [(2R,3R,5S)-5-[[[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-(2-cyanoethoxy)phosphoryl]oxymethyl]-2-(6-benzamidopurin-9-yl)oxolan-3-yl] benzoate
• 化学式: C₃₇H₃₆N₁₁O₁₁P
• 分子量: 841.734
• InChiKey: OANMJRSZZWJMCV-OKYLPUOISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  60
• 可旋转键数：
  17
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  250
• 氢给体数：
  2
• 氢受体数：
  17

反应信息

• 作为反应物：
  描述：

  β-cyanoethyl-3'-azido-3'-deoxy-5'-thymidinyl N⁶,O^2'-dibenzoyl-3'-deoxy-5'-adenosinyl phosphate 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 20.0h， 以92%的产率得到3'-azido-3'-deoxy-5'-thymidinyl 3'-deoxy-5'-adenosinyl phosphate sodium salt
  参考文献：
  名称：

  O-Alkyl-5',5'-dinucleoside phosphates as prodrugs of 3'-azidothymidine and cordycepin

  摘要：

  The syntheses of two O-alkyl-5',5'-dinucleoside phosphotriesters 2a and 2b as combined prodrugs of the antiviral drug AZT (1) and the antibiotic agent cordycepin (3) are described. 2a,b were obtained as a 1:1 diastereomeric mixture. The absolute configuration of the isolated diastereomers was determined by NOE NMR experiments and correlated with the migration characteristics on silica gel as well as the P-31-NMR chemical shift. The conformational features of 2b(R) and 2b(S) were determined m deuteriated dodecylphosphocholine micelles in aqueous solution using 2D-NOESY spectra and shown to be dependent on the configuration at phosphorus. Additionally, all new compounds were tested for their antiviral activities in HIV-1-infected CEM C113 and H9 cell systems. Although all compounds were able to significantly inhibit the HIV-1-induced cytopathogenic effect, only the phosphodiester 12 gave a selectivity index (SI(RT) = 2000) comparable to the reference compound AZT (1) (SI(RT) = 3000).

  DOI：

  10.1021/jo00052a053
• 作为产物：
  描述：

  N-(9-((2R,3R,5S)-5-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)-3-hydroxytetrahydrofuran-2-yl)-9H-purin-6-yl)benzamide 在 4-二甲氨基吡啶 四氮唑 、 碘 、 三乙胺 、 苯磺酸 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 2.33h， 生成 β-cyanoethyl-3'-azido-3'-deoxy-5'-thymidinyl N⁶,O^2'-dibenzoyl-3'-deoxy-5'-adenosinyl phosphate
  参考文献：
  名称：

  O-Alkyl-5',5'-dinucleoside phosphates as prodrugs of 3'-azidothymidine and cordycepin

  摘要：

  The syntheses of two O-alkyl-5',5'-dinucleoside phosphotriesters 2a and 2b as combined prodrugs of the antiviral drug AZT (1) and the antibiotic agent cordycepin (3) are described. 2a,b were obtained as a 1:1 diastereomeric mixture. The absolute configuration of the isolated diastereomers was determined by NOE NMR experiments and correlated with the migration characteristics on silica gel as well as the P-31-NMR chemical shift. The conformational features of 2b(R) and 2b(S) were determined m deuteriated dodecylphosphocholine micelles in aqueous solution using 2D-NOESY spectra and shown to be dependent on the configuration at phosphorus. Additionally, all new compounds were tested for their antiviral activities in HIV-1-infected CEM C113 and H9 cell systems. Although all compounds were able to significantly inhibit the HIV-1-induced cytopathogenic effect, only the phosphodiester 12 gave a selectivity index (SI(RT) = 2000) comparable to the reference compound AZT (1) (SI(RT) = 3000).

  DOI：

  10.1021/jo00052a053

文献信息

• O-Alkyl-5',5'-dinucleoside phosphates as prodrugs of 3'-azidothymidine and cordycepin
  作者：Chris Meier、Jean Michel Neumann、Francois Andre、Yvette Henin、Huynh Dinh Tam

  DOI：10.1021/jo00052a053

  日期：1992.12

  The syntheses of two O-alkyl-5',5'-dinucleoside phosphotriesters 2a and 2b as combined prodrugs of the antiviral drug AZT (1) and the antibiotic agent cordycepin (3) are described. 2a,b were obtained as a 1:1 diastereomeric mixture. The absolute configuration of the isolated diastereomers was determined by NOE NMR experiments and correlated with the migration characteristics on silica gel as well as the P-31-NMR chemical shift. The conformational features of 2b(R) and 2b(S) were determined m deuteriated dodecylphosphocholine micelles in aqueous solution using 2D-NOESY spectra and shown to be dependent on the configuration at phosphorus. Additionally, all new compounds were tested for their antiviral activities in HIV-1-infected CEM C113 and H9 cell systems. Although all compounds were able to significantly inhibit the HIV-1-induced cytopathogenic effect, only the phosphodiester 12 gave a selectivity index (SI(RT) = 2000) comparable to the reference compound AZT (1) (SI(RT) = 3000).