(2R,3R,4R,5R)-2-((((allyloxy)(3-((R)-4-((bis(2-cyanoethoxy)phosphoryl)oxy)-2-hydroxy-3,3-dimethylbutanamido)propoxy)phosphoryl)oxy)methyl)-5-(4-benzamido-2-oxopyrimidin-1(2H)-yl)tetrahydrofuran-3,4-diyl dibenzoate | 1196055-94-3

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物
• 英文名称: (2R,3R,4R,5R)-2-((((allyloxy)(3-((R)-4-((bis(2-cyanoethoxy)phosphoryl)oxy)-2-hydroxy-3,3-dimethylbutanamido)propoxy)phosphoryl)oxy)methyl)-5-(4-benzamido-2-oxopyrimidin-1(2H)-yl)tetrahydrofuran-3,4-diyl dibenzoate
• CAS: 1196055-94-3
• 化学式: C₄₈H₅₄N₆O₁₇P₂
• 分子量: 1048.93
• InChiKey: JIEXUOMWTYTIMO-ITDYDFKTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.07
• 重原子数：
  73.0
• 可旋转键数：
  29.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  312.25
• 氢给体数：
  3.0
• 氢受体数：
  21.0

反应信息

• 作为反应物：
  描述：

  (2R,3R,4R,5R)-2-((((allyloxy)(3-((R)-4-((bis(2-cyanoethoxy)phosphoryl)oxy)-2-hydroxy-3,3-dimethylbutanamido)propoxy)phosphoryl)oxy)methyl)-5-(4-benzamido-2-oxopyrimidin-1(2H)-yl)tetrahydrofuran-3,4-diyl dibenzoate 在 三甲基氯硅烷 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 ammonium hydroxide 、 2-巯基乙醇 、 sodium chloride 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 7.0h， 以80.8%的产率得到trisodium (R)-4-((3-(((((2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)oxidophosphoryk)oxy)propyl)amino)-3-hydroxy-2,2-dimethyl-4-oxobutyl phosphate
  参考文献：
  名称：

  Selective Inhibitors of Bacterial Phosphopantothenoylcysteine Synthetase

  摘要：

  Bacterial phosphopantothenotycysteine synthetase (PPCS) catalyzes the formation of phosphopantothenoylcysteine (PPC) from (R)-phosphopantothenate, L-cysteine, and cytidine-5'-triphosphate (CTP) and has been shown to be essential for growth and survival. The reaction proceeds through a phosphopantothenoyl cytidylate, mixed anhydride intermediate. Both structural and kinetic characterization studies on PPCS have shown differences in the nucleobase binding site between the bacterial and human enzyme. We report for the first time the design and synthesis of mimics of the phosphopantothenoyl cytidylate, which proved to be potent inhibitors of PPCS. These compounds were evaluated in vitro against PPCS from human and several species of bacteria and showed marked selectivity (up to 1000-fold) toward the bacterial. enzymes. A phosphodiester intermediate mimic was the most potent of the compounds synthesized and displayed stow-onset, tight-binding kinetics toward E. faecalis PPCS.

  DOI：

  10.1021/ja906537f
• 作为产物：
  描述：

  在 吡啶 、 (1R)-(-)-(8,8-dichloro-10-camphorsulfonyl) oxaziridine 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以55.6 mg的产率得到(2R,3R,4R,5R)-2-((((allyloxy)(3-((R)-4-((bis(2-cyanoethoxy)phosphoryl)oxy)-2-hydroxy-3,3-dimethylbutanamido)propoxy)phosphoryl)oxy)methyl)-5-(4-benzamido-2-oxopyrimidin-1(2H)-yl)tetrahydrofuran-3,4-diyl dibenzoate
  参考文献：
  名称：

  Selective Inhibitors of Bacterial Phosphopantothenoylcysteine Synthetase

  摘要：

  Bacterial phosphopantothenotycysteine synthetase (PPCS) catalyzes the formation of phosphopantothenoylcysteine (PPC) from (R)-phosphopantothenate, L-cysteine, and cytidine-5'-triphosphate (CTP) and has been shown to be essential for growth and survival. The reaction proceeds through a phosphopantothenoyl cytidylate, mixed anhydride intermediate. Both structural and kinetic characterization studies on PPCS have shown differences in the nucleobase binding site between the bacterial and human enzyme. We report for the first time the design and synthesis of mimics of the phosphopantothenoyl cytidylate, which proved to be potent inhibitors of PPCS. These compounds were evaluated in vitro against PPCS from human and several species of bacteria and showed marked selectivity (up to 1000-fold) toward the bacterial. enzymes. A phosphodiester intermediate mimic was the most potent of the compounds synthesized and displayed stow-onset, tight-binding kinetics toward E. faecalis PPCS.

  DOI：

  10.1021/ja906537f