[(2R,3S,5R)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)-2-[[1-phenyl-2-(pyridin-2-ylamino)ethoxy]carbonyloxymethyl]oxolan-3-yl] acetate | 648900-10-1

• 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-[[1-phenyl-2-(pyridin-2-ylamino)ethoxy]carbonyloxymethyl]oxolan-3-yl] acetate
• CAS: 648900-10-1
• 化学式: C₂₆H₂₈N₄O₈
• 分子量: 524.53
• InChiKey: LMSLATGKRZJKGD-ZNKCKFTLSA-N

物化性质

• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  38
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 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-[[1-phenyl-2-(pyridin-2-ylamino)ethoxy]carbonyloxymethyl]oxolan-3-yl] acetate 以 phosphate buffer 、 乙腈 为溶剂， 反应 1.0h， 生成 3-phenyl-2,3-dihydroimidazo[1,2-a]pyridine
  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：

  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-phenyl-2-(pyridin-2-ylamino)ethoxy]carbonyloxymethyl]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

文献信息

• Thermolabile hydroxyl protecting groups and methods of use
  申请人：Beaucage L. Serge

  公开号：US20060281911A1

  公开（公告）日：2006-12-14

  Provided is a hydroxyl-protected alcohol comprising a thermolabile hydroxyl-protecting group comprising a 2-pyridyl substituent and a precursor of the thermolabile hydroxyl-protected alcohol. An exemplary thermolabile hydroxyl-protected alcohol is represented by the formula Pg-O—R, wherein Pg is a protecting group of the formula: (Formula) wherein: A is a 2-pyridyl; Z is CH 2 or NR 1 ; R 1 , R 2 , R 2′ , R 3 and R 3′ are the same or different and each can be, e.g., H, alkyl, or alkyl comprising an aryl substituent; W is CO, CS, or SO; and R is the organic residue of the hydroxyl-protected alcohol. Also provided is a method of producing an alcohol, which method comprises heating the hydroxyl-protected alcohol, which optionally may be obtained from a precursor, at a temperature effective to cleave the hydroxyl-protecting group. The method can be used to produce oligonucleotides.
• US7612197B2
  申请人：——

  公开号：US7612197B2

  公开（公告）日：2009-11-03
• [EN] THERMOLABILE HYDROXYL PROTECTING GROUPS AND METHODS OF USE<br/>[FR] GROUPES PROTECTEURS HYDROXYLE THERMOLABILES ET LEURS PROCEDES D'UTILISATION
  申请人：US GOV HEALTH & HUMAN SERV

  公开号：WO2004101582A2

  公开（公告）日：2004-11-25

  Provided is a hydroxyl-protected alcohol comprising a thermolabile hydroxyl-protecting group comprising a 2-pyridyl substituent and a precursor of the thermolabile hydroxyl-protected alcohol. An exemplary thermolabile hydroxyl-protected alcohol is represented by the formula Pg-O-R, wherein Pg is a protecting group of the formula : (Formula) wherein : A is a 2-pyridyl; Z is CH2 or NR1; R1, R2, R2', R3 and R3' are the same or different and each can be, e.g., H, alkyl, or alkyl comprising an aryl substituent; W is CO, CS, or SO; and R is the organic residue of the hydroxyl-protected alcohol. Also provided is a method of producing an alcohol, which method comprises heating the hydroxyl-protected alcohol, which optionally may be obtained from a precursor, at a temperature effective to cleave the hydroxyl-protecting group. The method can be used to produce oligonucleotides.