1-{2-[(2R,4S)-2-(tert-Butyl-dimethyl-silanyloxymethyl)-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl}-5-methyl-1H-pyrimidine-2,4-dione | 202127-53-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 1-{2-[(2R,4S)-2-(tert-Butyl-dimethyl-silanyloxymethyl)-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl}-5-methyl-1H-pyrimidine-2,4-dione
• CAS: 202127-53-5
• 化学式: C₁₈H₃₁N₃O₅Si
• 分子量: 397.547
• InChiKey: COKLWUAMVUVPHM-KGLIPLIRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.83
• 重原子数：
  27.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  104.63
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  1-{2-[(2R,4S)-2-(tert-Butyl-dimethyl-silanyloxymethyl)-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl}-5-methyl-1H-pyrimidine-2,4-dione 在 吡啶 、 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 0.75h， 生成 1-(2-{(2R,4S)-2-Hydroxymethyl-4-[(4-methoxy-phenyl)-diphenyl-methoxy]-pyrrolidin-1-yl}-2-oxo-ethyl)-5-methyl-1H-pyrimidine-2,4-dione
  参考文献：
  名称：

  Oligonucleotide Analogues with 4-Hydroxy-N-Acetylprolinol as Sugar Substitute

  摘要：

  AbstractModified oligonucleotides incorporating trans‐4‐hydroxy‐N‐acetyl‐L‐prolinol (trans‐4‐HO‐L‐NAP) or its D‐analogue as sugar substitute were synthesised with adenine and thymine as nucleobases. All‐adenine oligonucleotides built from (2S,4S) or (2R,4R)‐cis‐4‐hydroxy‐N‐acetylprolinol were likewise prepared. Hybridisation studies revealed that heterocomplexes formed between polyU and homochiral trans‐4‐hydroxy‐N‐acetylprolinol‐based oligomers of the same as well as of opposite chirality (polyU/trans‐DA*13 and polyU/trans‐LA*13). The former, however, were triple‐stranded. Other complexes with ribonucleic acids were polyA/trans‐LT*13 and polyU/cis‐LA*13. Heteroduplexes with deoxynucleic acids were formed between trans‐LA*13 and oligothymidylate. Interaction was also observed for cis‐LA*13 and oligothymidylate, but not with the D‐hydroxyprolinol analogues. Microcalorimetry proved this interaction to be the formation of a triple‐stranded complex. Two heteroduplexes, trans‐LA*13/dT13 and trans‐LA*13/polyU, had similar or slightly increased stability when compared to the natural dA13/dT13 or dA13/polyU systems. Microcalorimetry clearly indicated the formation of a duplex, in contrast to interactions with N‐acetylprolinol oligonucleotides of different stereochemistry. Moreover, the enthalpy change was of the same magnitude but the association constant was slightly lower. Natural nucleic acids thus clearly prefer hybridisation with L‐hydroxyprolinol oligomers over D‐hydroxyprolinol oligomers. For the series investigated, the L‐trans oligomers (Figure 1) seem best to mimic natural oligonucleotides. These modified oligonucleotides formed homocomplexes if both strands were of the same chirality, that is, homocomplexes formed between trans‐LA* and trans‐LT* and between trans‐DA* and trans‐DT*, reflecting the isochiral pu‐py pairing found in natural nucleic acids. Once more, however, calorimetry proved these to be triplex interactions. Heterochiral pairing was not observed between modified oligonucleotides, but only between modified oligonucleotides and natural polyU. The thermal stabilities of these heterochiral complexes differed clearly.

  DOI：

  10.1002/chem.19970031215
• 作为产物：
  描述：

  cis-4-hydroxy-L-prolinol 在 N-甲基吗啉 、 咪唑 、 氨 、 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 50.08h， 生成 1-{2-[(2R,4S)-2-(tert-Butyl-dimethyl-silanyloxymethyl)-4-hydroxy-pyrrolidin-1-yl]-2-oxo-ethyl}-5-methyl-1H-pyrimidine-2,4-dione
  参考文献：
  名称：

  Oligonucleotide Analogues with 4-Hydroxy-N-Acetylprolinol as Sugar Substitute

  摘要：

  AbstractModified oligonucleotides incorporating trans‐4‐hydroxy‐N‐acetyl‐L‐prolinol (trans‐4‐HO‐L‐NAP) or its D‐analogue as sugar substitute were synthesised with adenine and thymine as nucleobases. All‐adenine oligonucleotides built from (2S,4S) or (2R,4R)‐cis‐4‐hydroxy‐N‐acetylprolinol were likewise prepared. Hybridisation studies revealed that heterocomplexes formed between polyU and homochiral trans‐4‐hydroxy‐N‐acetylprolinol‐based oligomers of the same as well as of opposite chirality (polyU/trans‐DA*13 and polyU/trans‐LA*13). The former, however, were triple‐stranded. Other complexes with ribonucleic acids were polyA/trans‐LT*13 and polyU/cis‐LA*13. Heteroduplexes with deoxynucleic acids were formed between trans‐LA*13 and oligothymidylate. Interaction was also observed for cis‐LA*13 and oligothymidylate, but not with the D‐hydroxyprolinol analogues. Microcalorimetry proved this interaction to be the formation of a triple‐stranded complex. Two heteroduplexes, trans‐LA*13/dT13 and trans‐LA*13/polyU, had similar or slightly increased stability when compared to the natural dA13/dT13 or dA13/polyU systems. Microcalorimetry clearly indicated the formation of a duplex, in contrast to interactions with N‐acetylprolinol oligonucleotides of different stereochemistry. Moreover, the enthalpy change was of the same magnitude but the association constant was slightly lower. Natural nucleic acids thus clearly prefer hybridisation with L‐hydroxyprolinol oligomers over D‐hydroxyprolinol oligomers. For the series investigated, the L‐trans oligomers (Figure 1) seem best to mimic natural oligonucleotides. These modified oligonucleotides formed homocomplexes if both strands were of the same chirality, that is, homocomplexes formed between trans‐LA* and trans‐LT* and between trans‐DA* and trans‐DT*, reflecting the isochiral pu‐py pairing found in natural nucleic acids. Once more, however, calorimetry proved these to be triplex interactions. Heterochiral pairing was not observed between modified oligonucleotides, but only between modified oligonucleotides and natural polyU. The thermal stabilities of these heterochiral complexes differed clearly.

  DOI：

  10.1002/chem.19970031215