1,2-O-isopropylidene-3(R)-(nicotinamid-6-ylmethyl)-α-D-ribofuranose | 175027-16-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 1,2-O-isopropylidene-3(R)-(nicotinamid-6-ylmethyl)-α-D-ribofuranose
• 英文别名: 6-[[(3aR,5R,6R,6aR)-6-hydroxy-5-(hydroxymethyl)-2,2-dimethyl-5,6a-dihydro-3aH-furo[2,3-d][1,3]dioxol-6-yl]methyl]pyridine-3-carboxamide
• CAS: 175027-16-4
• 化学式: C₁₅H₂₀N₂O₆
• 分子量: 324.334
• InChiKey: FRFWUNMAYLWFTL-NDPMZMCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.68
• 重原子数：
  23.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  124.13
• 氢给体数：
  3.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  1,2-O-isopropylidene-3(R)-(nicotinamid-6-ylmethyl)-α-D-ribofuranose 在 磷酸三乙酯 、 N,N'-羰基二咪唑 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 P¹-<1,2-O-isopropylidene-3(R)-(nicotinamid-6-ylmethyl)-α-D-ribofuranos-5-yl>-P²-(adenosin-5'-yl)pyrophosphate
  参考文献：
  名称：

  Synthesis of Methylene-Bridged Analogues of Nicotinamide Riboside, Nicotinamide Mononucleotide and Nicotinamide Adenine Dinucleotide

  摘要：

  5-O-tert-Butyldimethylsiyl-1,2-O-isopropylidene-3(R)-(nicotinamid-2-ylmethyl)-alpha-D-ribofuranose (11a) and -3(R)-(nicotinamid-6-ylmethyl)-alpha-D-ribofuranose (11b) were prepared by condensation of 5-O-terr-butyldimethylsilyl-1,2-O-isopropylidene-alpha-D-erythro-3-pentulofuranose (10) with lithiated (LDA) 2-methylnicotinamide and 6-methylnicotinamide, respectively, and then deprotected to give 1,2-O-isopropylidene-3-(R)-(nicotinamid-2-ylmethyl)-alpha-D- ribofuranose(12a)and1,2-O-isopropylidene3(R)-(nicotinamid-6-ylmethyl)-alpha-D-ribofuranose (12b). Benzoylation as well as phosphorylation of compounds 12 afforded the corresponding 5-O-benzoate (13b) and 5-O-monophosphates (14a and 14b). Treatment of 13b with CF3COOH/H2O caused 1,2-de-O-isopropylidenation with simultaneous cyclization to the corresponding methylene-bridged cyclic nucleoside - 3',6-methylene-1-(5-O-benzoyl-beta-D-ribofuranose)-3-carboxamidopyridinium trifluoro-acetate (8b) - restricted to the ''anti'' conformation. In a similar manner compounds 14a and 14b were converted into conformationally restricted 2,3'-methylene-1-(beta-D-ribofuranose)-3-carboxamidopyridinium-5'- monophosphate (9a - ''syn'') and 3',6-methylene-1-(beta-D-ribofuranose)-3-carboxamido - pyridinium-5'monophosphate (9b - ''anti'') respectively. Coupling of derivatives 12a and 12b with the adenosine 5'-methylenediphosphonate (16) afforded the corresponding dinucleotides 17. Upon acidic 1,2-de-O-isopropylidenation of 17b, the conformationally restricted P-1-[6,3'-methylene-1-(beta-D-ribofuranos-5-yl)-3-carboxamidopyridinium]-P-2-(adenosin-5'-yl)methylenediphosphonate 18b -''anti'' was formed. Compound 18b was found to be unstable. Upon addition of water 18b was converted into the anomeric mixture of acyclic dinucleotides, i.e. P-1-[3(R)-nicotinamid-6-ylmethyl-D-ribofuranos-5-yl]-P-2-(adenosin-5'-yl)-methylenediphosphonate (19b). In a similar manner, treatment of 17a with CF2COOH/H2O and HPLC purification afforded the corresponding dinucleotide 19a.

  DOI：

  10.1080/07328319608002377
• 作为产物：
  描述：

  1,2-O-isopropylidene-5-O-tert-butyldimethylsilyl-3(R)-(nicotinamid-6-ylmethyl)-α-D-ribofuranose 在 溶剂黄146 作用下， 反应 5.0h， 以98%的产率得到1,2-O-isopropylidene-3(R)-(nicotinamid-6-ylmethyl)-α-D-ribofuranose
  参考文献：
  名称：

  Synthesis of Methylene-Bridged Analogues of Nicotinamide Riboside, Nicotinamide Mononucleotide and Nicotinamide Adenine Dinucleotide

  摘要：

  5-O-tert-Butyldimethylsiyl-1,2-O-isopropylidene-3(R)-(nicotinamid-2-ylmethyl)-alpha-D-ribofuranose (11a) and -3(R)-(nicotinamid-6-ylmethyl)-alpha-D-ribofuranose (11b) were prepared by condensation of 5-O-terr-butyldimethylsilyl-1,2-O-isopropylidene-alpha-D-erythro-3-pentulofuranose (10) with lithiated (LDA) 2-methylnicotinamide and 6-methylnicotinamide, respectively, and then deprotected to give 1,2-O-isopropylidene-3-(R)-(nicotinamid-2-ylmethyl)-alpha-D- ribofuranose(12a)and1,2-O-isopropylidene3(R)-(nicotinamid-6-ylmethyl)-alpha-D-ribofuranose (12b). Benzoylation as well as phosphorylation of compounds 12 afforded the corresponding 5-O-benzoate (13b) and 5-O-monophosphates (14a and 14b). Treatment of 13b with CF3COOH/H2O caused 1,2-de-O-isopropylidenation with simultaneous cyclization to the corresponding methylene-bridged cyclic nucleoside - 3',6-methylene-1-(5-O-benzoyl-beta-D-ribofuranose)-3-carboxamidopyridinium trifluoro-acetate (8b) - restricted to the ''anti'' conformation. In a similar manner compounds 14a and 14b were converted into conformationally restricted 2,3'-methylene-1-(beta-D-ribofuranose)-3-carboxamidopyridinium-5'- monophosphate (9a - ''syn'') and 3',6-methylene-1-(beta-D-ribofuranose)-3-carboxamido - pyridinium-5'monophosphate (9b - ''anti'') respectively. Coupling of derivatives 12a and 12b with the adenosine 5'-methylenediphosphonate (16) afforded the corresponding dinucleotides 17. Upon acidic 1,2-de-O-isopropylidenation of 17b, the conformationally restricted P-1-[6,3'-methylene-1-(beta-D-ribofuranos-5-yl)-3-carboxamidopyridinium]-P-2-(adenosin-5'-yl)methylenediphosphonate 18b -''anti'' was formed. Compound 18b was found to be unstable. Upon addition of water 18b was converted into the anomeric mixture of acyclic dinucleotides, i.e. P-1-[3(R)-nicotinamid-6-ylmethyl-D-ribofuranos-5-yl]-P-2-(adenosin-5'-yl)-methylenediphosphonate (19b). In a similar manner, treatment of 17a with CF2COOH/H2O and HPLC purification afforded the corresponding dinucleotide 19a.

  DOI：

  10.1080/07328319608002377