[(2R,3S,5R)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)-2-[2-(pyridin-2-ylamino)ethoxycarbonyloxymethyl]oxolan-3-yl] acetate | 648900-05-4

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: [(2R,3S,5R)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)-2-[2-(pyridin-2-ylamino)ethoxycarbonyloxymethyl]oxolan-3-yl] acetate
• CAS: 648900-05-4
• 化学式: C₂₀H₂₄N₄O₈
• 分子量: 448.433
• InChiKey: RXCKBLIJAXELQQ-ZMSDIMECSA-N

物化性质

• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  32
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  145
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  [(2R,3S,5R)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)-2-[2-(pyridin-2-ylamino)ethoxycarbonyloxymethyl]oxolan-3-yl] acetate 在 四甲基胍 作用下， 以 phosphate buffer 、 乙腈 为溶剂， 反应 7.0h， 生成 5'-O-(1-butyl)oxycarbonyl-3'-O-acetylthymidine
  参考文献：
  名称：

  Thermolytic Carbonates for Potential 5‘-Hydroxyl Protection of Deoxyribonucleosides

  摘要：

  Thermolytic groups structurally related to well-studied heat-sensitive phosphate/thiophosphate protecting groups have been evaluated for 5'-hydroxyl protection of deoxyribonucleosides as carbonates and for potential use in solid-phase oligonucleotide synthesis. The spatial arrangement of selected functional groups forming an asymmetric nucleosidic 5'-O-carbonic acid ester has been designed to enable heat-induced cyclodecarbonation reactions, which would result in the release of carbon dioxide and the generation of a nucleosidic 5'-hydroxyl group. The nucleosidic 5'-O-carbonates 3-8, 10-15, and 19-21 were prepared and were isolated in yields ranging from 45 to 83%. Thermolytic deprotection of these carbonates is preferably performed in aqueous organic solvent at 90 degreesC under near neutral conditions. The rates of carbonate deprotection are dependent on the nucleophilicity of the functional group involved in the postulated cyclodecarbonation reaction and on solvent polarity. Deprotection kinetics increase according to the following order: 4 < 5 < 10 < 6 < 12 < 7 < 13 < 8 < 14 congruent to 19-21 and CCl4 < dioxane < MeCN < t-BuOH < MeCN:phosphate buffer (3:1 v/v, pH 7.0) < EtOH:phosphate buffer (1:1 v/v, pH 7.0). Complete thermolytic deprotection of carbonates 7, 8, 13, and 14 is achieved within 20 min to 2 h under optimal conditions in phosphate buffer-MeCN. The 2-(2-pyridyl)amino-1-phenylethyl and 2-[N-methyl-N-(2-pyridyl)]aminoethyl groups are particularly promising for 5'-hydroxyl protection of deoxyribonucleosides as thermolytic carbonates.

  DOI：

  10.1021/jo035089g
• 作为产物：
  描述：

  2-(吡啶-2-基氨基)乙醇 、 3'-O-acetylthymidine 5'-O-(1-imidazolyl)carbamate 在 四甲基胍 作用下， 以 乙腈 为溶剂， 反应 2.0h， 生成 [(2R,3S,5R)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)-2-[2-(pyridin-2-ylamino)ethoxycarbonyloxymethyl]oxolan-3-yl] acetate
  参考文献：
  名称：

  Thermolytic Carbonates for Potential 5‘-Hydroxyl Protection of Deoxyribonucleosides

  摘要：

  Thermolytic groups structurally related to well-studied heat-sensitive phosphate/thiophosphate protecting groups have been evaluated for 5'-hydroxyl protection of deoxyribonucleosides as carbonates and for potential use in solid-phase oligonucleotide synthesis. The spatial arrangement of selected functional groups forming an asymmetric nucleosidic 5'-O-carbonic acid ester has been designed to enable heat-induced cyclodecarbonation reactions, which would result in the release of carbon dioxide and the generation of a nucleosidic 5'-hydroxyl group. The nucleosidic 5'-O-carbonates 3-8, 10-15, and 19-21 were prepared and were isolated in yields ranging from 45 to 83%. Thermolytic deprotection of these carbonates is preferably performed in aqueous organic solvent at 90 degreesC under near neutral conditions. The rates of carbonate deprotection are dependent on the nucleophilicity of the functional group involved in the postulated cyclodecarbonation reaction and on solvent polarity. Deprotection kinetics increase according to the following order: 4 < 5 < 10 < 6 < 12 < 7 < 13 < 8 < 14 congruent to 19-21 and CCl4 < dioxane < MeCN < t-BuOH < MeCN:phosphate buffer (3:1 v/v, pH 7.0) < EtOH:phosphate buffer (1:1 v/v, pH 7.0). Complete thermolytic deprotection of carbonates 7, 8, 13, and 14 is achieved within 20 min to 2 h under optimal conditions in phosphate buffer-MeCN. The 2-(2-pyridyl)amino-1-phenylethyl and 2-[N-methyl-N-(2-pyridyl)]aminoethyl groups are particularly promising for 5'-hydroxyl protection of deoxyribonucleosides as thermolytic carbonates.

  DOI：

  10.1021/jo035089g