(3aR,4R,6aS)-2,2-Dimethyl-4-phosphonooxymethyl-tetrahydro-[1,3]dioxolo[4,5-c]pyrrole-5-carboxylic acid benzyl ester | 1053262-99-9

• 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: (3aR,4R,6aS)-2,2-Dimethyl-4-phosphonooxymethyl-tetrahydro-[1,3]dioxolo[4,5-c]pyrrole-5-carboxylic acid benzyl ester
• 英文别名: benzyl (3aR,4R,6aS)-2,2-dimethyl-4-(phosphonooxymethyl)-3a,4,6,6a-tetrahydro-[1,3]dioxolo[4,5-c]pyrrole-5-carboxylate
• CAS: 1053262-99-9
• 化学式: C₁₆H₂₂NO₈P
• 分子量: 387.326
• InChiKey: AORWENXMWSOUIZ-HZSPNIEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (3aR,4R,6aS)-2,2-Dimethyl-4-phosphonooxymethyl-tetrahydro-[1,3]dioxolo[4,5-c]pyrrole-5-carboxylic acid benzyl ester 在 盐酸 作用下， 以 乙腈 为溶剂， 反应 0.75h， 以0.51 g的产率得到(2R,3R,4S)-1-(benzyloxycarbonyl)-2-<(phosphooxy)methyl>pyrrolidine-3,4-diol
  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 、 水 、 三氯氧磷 作用下， 以 乙腈 为溶剂， 反应 2.0h， 生成 (3aR,4R,6aS)-2,2-Dimethyl-4-phosphonooxymethyl-tetrahydro-[1,3]dioxolo[4,5-c]pyrrole-5-carboxylic acid benzyl ester
  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