3'-O-acetylthymidine 5'-O-(1-imidazolyl)carbamate | 1053653-67-0

• 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: 3'-O-acetylthymidine 5'-O-(1-imidazolyl)carbamate
• 英文别名: [(2R,3S,5R)-3-acetyloxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl imidazole-1-carboxylate
• CAS: 1053653-67-0
• 化学式: C₁₆H₁₈N₄O₇
• 分子量: 378.342
• InChiKey: JENWMOXADDSGQY-YNEHKIRRSA-N

物化性质

• 密度：
  1.56±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  129
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3'-O-acetylthymidine 5'-O-(1-imidazolyl)carbamate 在 四甲基胍 作用下， 以 phosphate buffer 、 乙腈 为溶剂， 反应 6.0h， 生成 [(2R,3S,5R)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)-2-(1-phenylbutoxycarbonyloxymethyl)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
• 作为产物：
  描述：

  [(2R,3S,5R)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)-2-[2-(pyridin-2-ylamino)ethoxycarbonyloxymethyl]oxolan-3-yl] acetate 以 phosphate buffer 、 乙腈 为溶剂， 反应 5.0h， 生成 3'-O-acetylthymidine 5'-O-(1-imidazolyl)carbamate
  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

文献信息

• [EN] THERMALLY-CLEAVABLE PROTECTING AND LINKER GROUPS<br/>[FR] GROUPES PROTECTEURS ET DE LIAISON THERMIQUEMENT CLIVABLES
  申请人：EVONETIX LTD

  公开号：WO2018189546A1

  公开（公告）日：2018-10-18

  The present invention relates to chemical linkers and protecting groups, compounds and compositions containing the chemical linkers or protecting groups, and intermediates and processes that can be used to prepare them. The chemical linkers and protecting groups are based on pyrrolidine and piperidine activating groups, which undergo intramolecular cyclisation upon heating with release of carbon dioxide, thereby releasing the organic compound from a substrate. In particular, those chemical linkers and protecting groups are useful in the solid phase synthesis of oligonucleotides according to the following representative schemes.

  本发明涉及化学连接剂和保护基团，含有化学连接剂或保护基团的化合物和组合物，以及可用于制备它们的中间体和过程。这些化学连接剂和保护基团基于吡咯烷和哌哆啶活化基团，加热后发生分子内环化，并释放二氧化碳，从而释放有机化合物从底物中。特别是，这些化学连接剂和保护基团在寡核苷酸的固相合成中具有用途，具体方案如下。
• Novel thermolabile protecting groups with higher stability at ambient temperature
  作者：Marcin K. Chmielewski

  DOI：10.1016/j.tetlet.2011.11.122

  日期：2012.2

  Novel thermolabile hydroxyl protecting groups of increased thermostability are proposed. The stability of these groups at different temperatures ranges has been determined. The 2-pyridyl-N-(2,4-difluorobenzyl)aminoethyl unit was selected as stable at ambient temperature and very labile at increased temperature. The half-life times for the best groups were established. Application of this chemistry to

  提出了增加热稳定性的新型热不稳定羟基保护基。已经确定了这些基团在不同温度范围内的稳定性。选择2-吡啶基-N-（2，4-二氟苄基）氨基乙基单元在环境温度下稳定并且在升高的温度下非常不稳定。确定了最佳组的半衰期。还证明了该化学方法在保护胸苷的不同羟基上的应用。