Phosphoric acid mono-[(2R,3S,4R,5S)-5-(6-carbamoyl-pyridin-2-yl)-3,4-dihydroxy-tetrahydro-furan-2-ylmethyl] ester | 168014-82-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: Phosphoric acid mono-[(2R,3S,4R,5S)-5-(6-carbamoyl-pyridin-2-yl)-3,4-dihydroxy-tetrahydro-furan-2-ylmethyl] ester
• CAS: 168014-82-2
• 化学式: C₁₁H₁₅N₂O₈P
• 分子量: 334.222
• InChiKey: AYMUAGAUATXOHK-KYXWUPHJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.55
• 重原子数：
  22.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  172.43
• 氢给体数：
  5.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  Phosphoric acid mono-[(2R,3S,4R,5S)-5-(6-carbamoyl-pyridin-2-yl)-3,4-dihydroxy-tetrahydro-furan-2-ylmethyl] ester 在 三正丁胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 72.0h， 生成 6-(β-D-ribofuranosyl)picolinamide-(5'-5'')-adenosine pyrophosphate
  参考文献：
  名称：

  NAD analogs. 1. Synthesis of isosteric analogs of nicotinamide adenine dinucleotide containing C-nucleotide of nicotinamide or picolinamide

  摘要：

  Two isosteric analogues of nicotinamide adenine dinucleotide, C-NAD (11) and C-PAD (12), in which the nicotinamide riboside portion is replaced by a C-nucleoside, were synthesized from 5-(beta-D-ribofuranosyl)nicotinamide (7) and 6-(beta-D-ribofuranosyl)picolinamide (8), respectively. Nucleoside 7 was prepared from the 2,3-O-isopropylidene-5-O-(tetrahydropyranyl)-D-ribonolactone (13) and 3-cyano-5-lithiopyridine as reported earlier. Nucleoside 8 was obtained by conversion of the bromo function of the 6-(2,3:4,5-di-O-isopropylidene-D-altro-pentitol-1-yl)-2-bromopyridine (14) into a carboxamido group followed by mesylation of the anomeric hydroxyl group to give derivative 18. Treatment of 18 with CF3COOH/CHCl3 caused deisopropylidenation with simultaneous cyclization into the desired 6-(beta-D-ribofuranosyl)picolinamide (8). NAD analogues, C-NAD (11) and C-PAD (12), were synthesized by imidazole-catalyzed coupling of the corresponding 5'-monophosphates of 7 and 8 with the adenosine-5'-monophosphate. Dinucleotide 11 was found to inhibit the proliferation of L1210 cells (IC50 = 7 muM) and to be a good competitive inhibitor of inosine monophosphate dehydrogenase (IMPDH, ID50 = 20 muM) as well as bovine glutamate dehydrogenase (GDH, K(i) = 15 muM). Interestingly, C-NAD (11) caused extremely potent noncompetitive inhibition of horse liver alcohol dehydrogenase (ADH, K(i) = 1.1 nM), whereas C-PAD (12) was found to be a much less potent competitive inhibitor (K(i) = 20 muM) of ADH.

  DOI：

  10.1021/jm00065a008
• 作为产物：
  描述：

  6-(2,3:4,5-di-O-isopropylidene-D-altro-pentitol-1-yl)picolinamide 在 4-二甲氨基吡啶 、 三乙胺 、 三氟乙酸 、 三氯氧磷 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 反应 9.0h， 生成 Phosphoric acid mono-[(2R,3S,4R,5S)-5-(6-carbamoyl-pyridin-2-yl)-3,4-dihydroxy-tetrahydro-furan-2-ylmethyl] ester
  参考文献：
  名称：

  NAD analogs. 1. Synthesis of isosteric analogs of nicotinamide adenine dinucleotide containing C-nucleotide of nicotinamide or picolinamide

  摘要：

  Two isosteric analogues of nicotinamide adenine dinucleotide, C-NAD (11) and C-PAD (12), in which the nicotinamide riboside portion is replaced by a C-nucleoside, were synthesized from 5-(beta-D-ribofuranosyl)nicotinamide (7) and 6-(beta-D-ribofuranosyl)picolinamide (8), respectively. Nucleoside 7 was prepared from the 2,3-O-isopropylidene-5-O-(tetrahydropyranyl)-D-ribonolactone (13) and 3-cyano-5-lithiopyridine as reported earlier. Nucleoside 8 was obtained by conversion of the bromo function of the 6-(2,3:4,5-di-O-isopropylidene-D-altro-pentitol-1-yl)-2-bromopyridine (14) into a carboxamido group followed by mesylation of the anomeric hydroxyl group to give derivative 18. Treatment of 18 with CF3COOH/CHCl3 caused deisopropylidenation with simultaneous cyclization into the desired 6-(beta-D-ribofuranosyl)picolinamide (8). NAD analogues, C-NAD (11) and C-PAD (12), were synthesized by imidazole-catalyzed coupling of the corresponding 5'-monophosphates of 7 and 8 with the adenosine-5'-monophosphate. Dinucleotide 11 was found to inhibit the proliferation of L1210 cells (IC50 = 7 muM) and to be a good competitive inhibitor of inosine monophosphate dehydrogenase (IMPDH, ID50 = 20 muM) as well as bovine glutamate dehydrogenase (GDH, K(i) = 15 muM). Interestingly, C-NAD (11) caused extremely potent noncompetitive inhibition of horse liver alcohol dehydrogenase (ADH, K(i) = 1.1 nM), whereas C-PAD (12) was found to be a much less potent competitive inhibitor (K(i) = 20 muM) of ADH.

  DOI：

  10.1021/jm00065a008