benzyl (2R,3R,4S)-2-[[[[(2R,3S,4R,5R)-5-[6-(benzylamino)purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]oxymethyl]-3,4-dihydroxypyrrolidine-1-carboxylate | 1055041-51-4

• 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: benzyl (2R,3R,4S)-2-[[[[(2R,3S,4R,5R)-5-[6-(benzylamino)purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]oxymethyl]-3,4-dihydroxypyrrolidine-1-carboxylate
• CAS: 1055041-51-4
• 化学式: C₃₀H₃₆N₆O₁₄P₂
• 分子量: 766.595
• InChiKey: XEQLDKJMWIGFCJ-VZEBNISZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  52
• 可旋转键数：
  15
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  278
• 氢给体数：
  7
• 氢受体数：
  18

反应信息

• 作为反应物：
  描述：

  benzyl (2R,3R,4S)-2-[[[[(2R,3S,4R,5R)-5-[6-(benzylamino)purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]oxymethyl]-3,4-dihydroxypyrrolidine-1-carboxylate 在 palladium on activated charcoal 氢气 作用下， 生成 [[(2R,3S,4R,5R)-5-[6-(benzylamino)purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2R,3R,4S)-3,4-dihydroxypyrrolidin-2-yl]methyl hydrogen phosphate
  参考文献：
  名称：

  SAR Analysis of Adenosine Diphosphate (Hydroxymethyl)pyrrolidinediol Inhibition of Poly(ADP-ribose) Glycohydrolase

  摘要：

  Polyadenosine diphosphoribose glycohydrolase (PARG) catalyzes the intracellular hydrolysis of adenosine diphosphoribose polymers. Because structure-activity data are lacking for PARG, the specific inhibitor adenosine diphosphate (hydroxymethyl)pyrrolidinediol (ADP-HPD) was utilized to determine the effects of structure on inhibitor potency using PARG isolated from bovine thymus (bPARG) and recombinant bovine PARG catalytic fragment (rPARG-CF). Both enzymes were strongly inhibited by submicromolar levels of ADP-HPD, but ADP and the phosphorylated pyrrolidine displayed no activity. Utilizing ADP-HPD analogues containing 2-, N-6, or 8-adenosyl substituents or guanine instead of adenine, the importance of adenine ring recognition as well as a correlation between loss of PARG inhibition and the length and bulkiness of 8-adenosyl substituents was shown. Utilization of ADP-HPD analogues lacking one or both pyrrolidine cis-hydroxyls demonstrated their importance for inhibitor binding. Last, the similarity between naturally occurring bPARG and heterologously expressed rPARG-CF was demonstrated. Therefore, readily available rPARG-CF is suitable for use in future studies to determine the structural aspects of PARG.

  DOI：

  10.1021/jm020541u
• 作为产物：
  描述：

  (2R,3R,4S)-1-(benzyloxycarbonyl)-2-(hydroxymethyl)pyrrolidine-3,4-diol 3,4-O-isopropylidene acetal 在 吡啶 、 盐酸 、 水 、 三氯氧磷 作用下， 以 乙腈 为溶剂， 反应 2.75h， 生成 benzyl (2R,3R,4S)-2-[[[[(2R,3S,4R,5R)-5-[6-(benzylamino)purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]oxymethyl]-3,4-dihydroxypyrrolidine-1-carboxylate
  参考文献：
  名称：

  SAR Analysis of Adenosine Diphosphate (Hydroxymethyl)pyrrolidinediol Inhibition of Poly(ADP-ribose) Glycohydrolase

  摘要：

  Polyadenosine diphosphoribose glycohydrolase (PARG) catalyzes the intracellular hydrolysis of adenosine diphosphoribose polymers. Because structure-activity data are lacking for PARG, the specific inhibitor adenosine diphosphate (hydroxymethyl)pyrrolidinediol (ADP-HPD) was utilized to determine the effects of structure on inhibitor potency using PARG isolated from bovine thymus (bPARG) and recombinant bovine PARG catalytic fragment (rPARG-CF). Both enzymes were strongly inhibited by submicromolar levels of ADP-HPD, but ADP and the phosphorylated pyrrolidine displayed no activity. Utilizing ADP-HPD analogues containing 2-, N-6, or 8-adenosyl substituents or guanine instead of adenine, the importance of adenine ring recognition as well as a correlation between loss of PARG inhibition and the length and bulkiness of 8-adenosyl substituents was shown. Utilization of ADP-HPD analogues lacking one or both pyrrolidine cis-hydroxyls demonstrated their importance for inhibitor binding. Last, the similarity between naturally occurring bPARG and heterologously expressed rPARG-CF was demonstrated. Therefore, readily available rPARG-CF is suitable for use in future studies to determine the structural aspects of PARG.

  DOI：

  10.1021/jm020541u