Benzoic acid (2R,3R,5S)-5-[[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-2-ylmethoxy]-(2-cyano-ethoxy)-phosphanyloxymethyl]-2-(6-benzoylamino-purin-9-yl)-tetrahydro-furan-3-yl ester | 138824-83-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: Benzoic acid (2R,3R,5S)-5-[[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-2-ylmethoxy]-(2-cyano-ethoxy)-phosphanyloxymethyl]-2-(6-benzoylamino-purin-9-yl)-tetrahydro-furan-3-yl ester
• 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)phosphanyl]oxymethyl]-2-(6-benzamidopurin-9-yl)oxolan-3-yl] benzoate
• CAS: 138824-83-6
• 化学式: C₃₇H₃₆N₁₁O₁₀P
• 分子量: 825.734
• InChiKey: RHIVNQSEUUFGRV-DYESHGEUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  59
• 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：
  233
• 氢给体数：
  2
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  Benzoic acid (2R,3R,5S)-5-[[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-2-ylmethoxy]-(2-cyano-ethoxy)-phosphanyloxymethyl]-2-(6-benzoylamino-purin-9-yl)-tetrahydro-furan-3-yl ester 在 碘 、 sodium methylate 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 水 、 乙腈 为溶剂， 反应 40.08h， 生成 hexadecanyl 3'-azido-3'-deoxy-5'-thymidinyl 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
• 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 、 三乙胺 、 苯磺酸 作用下， 以 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 2.25h， 生成 Benzoic acid (2R,3R,5S)-5-[[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-2-ylmethoxy]-(2-cyano-ethoxy)-phosphanyloxymethyl]-2-(6-benzoylamino-purin-9-yl)-tetrahydro-furan-3-yl ester
  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