3-methyl-2-(N-phenoxyacetylamino)-5-(2',3,',5'-tri-O-benzyl-β-D-ribofuranosyl)pyridine | 190908-02-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-methyl-2-(N-phenoxyacetylamino)-5-(2',3,',5'-tri-O-benzyl-β-D-ribofuranosyl)pyridine
• CAS: 190908-02-2
• 化学式: C₄₀H₄₀N₂O₆
• 分子量: 644.767
• InChiKey: BNFPUYDVXJUMKG-ZACWFTDDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.24
• 重原子数：
  48.0
• 可旋转键数：
  15.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  88.14
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  3-methyl-2-(N-phenoxyacetylamino)-5-(2',3,',5'-tri-O-benzyl-β-D-ribofuranosyl)pyridine 在 三溴化硼 作用下， 以 吡啶 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 13.5h， 生成 3-methyl-2-[N-(phenoxyacetyl)amino]-5-[3',5'-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-2'-O-(imidazolyl thiocarbonyl)-β-D-ribofuranosyl]pyridine
  参考文献：
  名称：

  5-Substituted 2-Aminopyridine C-Nucleosides as Protonated Cytidine Equivalents:  Increasing Efficiency and Selectivity in DNA Triple-Helix Formation

  摘要：

  The easily accessible C-nucleoside 2-amino-5-(2'-deoxy-beta-D-ribofuranosyl)py (P) and its 3-methyl (P-Me) and 2'-O-methyl (P-OMe) derivatives were synthesized and incorporated as protonated cytidine equivalents in homopyrimidine oligodeoxynucleotides. T-m measurements indicate that oligonucleotides containing P or P-Me have a higher affinity to double-stranded DNA over the pH range of 6-8 than, 5-methylcytidine (C-Me) containing oligonucleotides. This increase in stability is most pronounced above pH 7.0. The average increase in T-m/modification for the dissociation of oligonucleotide d((TTTTTPTPTPTPTPT)-P-Me-P-Me-P-Me-P-Me-P-Me) from a 21-mer target duplex at pH 7.5 is 2.3 degrees C relative to oligonucleotide. d((TTTTTCTCTCTCTCT)-C-Me-C-Me-C-Me-C-Me-C-Me). The pH dependence and sequence composition effects are much less pronounced for P-Me (and also P) containing oligonucleotides than for C-Me containing ones. While oligonucleotide d((TTTCCCCTTTTCTTT)-C-Me-C-Me-C-Me-C-Me-C-Me) shows no longer any affinity to the target duplex above pH 6.5, oligonucleotide d((TTTPPPPTTTTPTTT)-P-Me-P-Me-P-Me-P-Me-P-Me) displays preserved binding with a T-m of 32.5 degrees C at pH 7.0 and even binds with a T-m of 23.3 degrees C at pH 8.0. Oligonucleotides containing P-OMe show distinctly less stable triple helices. The average decrease in T-m/modification for oligonucleotide d(TTTPTPOMeTPOMeTPOMeTPOMeTPOMeT) at pH 6.5 is 6.7 degrees C relative to the C-Me containing oligonucleotide. DNase I footprint titration experiments indicate that d((TTTTTPTPTPTPTPT)-P-Me-P-Me-P-Me-P-Me-P-Me) binds not only five times stronger to a 229 base pair DNA fragment than d((TTTTTCTCTCTCTCT)-C-Me-C-Me-C-Me-C-Me-C-Me) but also with higher selectivity; UV-melting experiments show that duplexes of d(TTTTTCTXTCTCTCT) (where X = P, P-Me, or P-OMe) With their antiparallel Watson-Crick complement are dramatically less stable (Delta T-m < -12 degrees C) at pH 8.0 than the corresponding natural duplex. Thus the new bases P and P-Me show Hoogsteen specific pairing behavior.

  DOI：

  10.1021/ja9704904
• 作为产物：
  描述：

  2-氨基-3-甲基-5-溴吡啶 在 三乙基硅烷 、 正丁基锂 、 三氟化硼乙醚 、 zinc(II) iodide 作用下， 以 吡啶 为溶剂， 反应 26.5h， 生成 3-methyl-2-(N-phenoxyacetylamino)-5-(2',3,',5'-tri-O-benzyl-β-D-ribofuranosyl)pyridine
  参考文献：
  名称：

  5-Substituted 2-Aminopyridine C-Nucleosides as Protonated Cytidine Equivalents:  Increasing Efficiency and Selectivity in DNA Triple-Helix Formation

  摘要：

  The easily accessible C-nucleoside 2-amino-5-(2'-deoxy-beta-D-ribofuranosyl)py (P) and its 3-methyl (P-Me) and 2'-O-methyl (P-OMe) derivatives were synthesized and incorporated as protonated cytidine equivalents in homopyrimidine oligodeoxynucleotides. T-m measurements indicate that oligonucleotides containing P or P-Me have a higher affinity to double-stranded DNA over the pH range of 6-8 than, 5-methylcytidine (C-Me) containing oligonucleotides. This increase in stability is most pronounced above pH 7.0. The average increase in T-m/modification for the dissociation of oligonucleotide d((TTTTTPTPTPTPTPT)-P-Me-P-Me-P-Me-P-Me-P-Me) from a 21-mer target duplex at pH 7.5 is 2.3 degrees C relative to oligonucleotide. d((TTTTTCTCTCTCTCT)-C-Me-C-Me-C-Me-C-Me-C-Me). The pH dependence and sequence composition effects are much less pronounced for P-Me (and also P) containing oligonucleotides than for C-Me containing ones. While oligonucleotide d((TTTCCCCTTTTCTTT)-C-Me-C-Me-C-Me-C-Me-C-Me) shows no longer any affinity to the target duplex above pH 6.5, oligonucleotide d((TTTPPPPTTTTPTTT)-P-Me-P-Me-P-Me-P-Me-P-Me) displays preserved binding with a T-m of 32.5 degrees C at pH 7.0 and even binds with a T-m of 23.3 degrees C at pH 8.0. Oligonucleotides containing P-OMe show distinctly less stable triple helices. The average decrease in T-m/modification for oligonucleotide d(TTTPTPOMeTPOMeTPOMeTPOMeTPOMeT) at pH 6.5 is 6.7 degrees C relative to the C-Me containing oligonucleotide. DNase I footprint titration experiments indicate that d((TTTTTPTPTPTPTPT)-P-Me-P-Me-P-Me-P-Me-P-Me) binds not only five times stronger to a 229 base pair DNA fragment than d((TTTTTCTCTCTCTCT)-C-Me-C-Me-C-Me-C-Me-C-Me) but also with higher selectivity; UV-melting experiments show that duplexes of d(TTTTTCTXTCTCTCT) (where X = P, P-Me, or P-OMe) With their antiparallel Watson-Crick complement are dramatically less stable (Delta T-m < -12 degrees C) at pH 8.0 than the corresponding natural duplex. Thus the new bases P and P-Me show Hoogsteen specific pairing behavior.

  DOI：

  10.1021/ja9704904

文献信息

• 5-Substituted 2-Aminopyridine <i>C</i>-Nucleosides as Protonated Cytidine Equivalents:  Increasing Efficiency and Selectivity in DNA Triple-Helix Formation
  作者：Stefan Hildbrand、Adrian Blaser、Serge P. Parel、Christian J. Leumann

  DOI：10.1021/ja9704904

  日期：1997.6.1

  The easily accessible C-nucleoside 2-amino-5-(2'-deoxy-beta-D-ribofuranosyl)py (P) and its 3-methyl (P-Me) and 2'-O-methyl (P-OMe) derivatives were synthesized and incorporated as protonated cytidine equivalents in homopyrimidine oligodeoxynucleotides. T-m measurements indicate that oligonucleotides containing P or P-Me have a higher affinity to double-stranded DNA over the pH range of 6-8 than, 5-methylcytidine (C-Me) containing oligonucleotides. This increase in stability is most pronounced above pH 7.0. The average increase in T-m/modification for the dissociation of oligonucleotide d((TTTTTPTPTPTPTPT)-P-Me-P-Me-P-Me-P-Me-P-Me) from a 21-mer target duplex at pH 7.5 is 2.3 degrees C relative to oligonucleotide. d((TTTTTCTCTCTCTCT)-C-Me-C-Me-C-Me-C-Me-C-Me). The pH dependence and sequence composition effects are much less pronounced for P-Me (and also P) containing oligonucleotides than for C-Me containing ones. While oligonucleotide d((TTTCCCCTTTTCTTT)-C-Me-C-Me-C-Me-C-Me-C-Me) shows no longer any affinity to the target duplex above pH 6.5, oligonucleotide d((TTTPPPPTTTTPTTT)-P-Me-P-Me-P-Me-P-Me-P-Me) displays preserved binding with a T-m of 32.5 degrees C at pH 7.0 and even binds with a T-m of 23.3 degrees C at pH 8.0. Oligonucleotides containing P-OMe show distinctly less stable triple helices. The average decrease in T-m/modification for oligonucleotide d(TTTPTPOMeTPOMeTPOMeTPOMeTPOMeT) at pH 6.5 is 6.7 degrees C relative to the C-Me containing oligonucleotide. DNase I footprint titration experiments indicate that d((TTTTTPTPTPTPTPT)-P-Me-P-Me-P-Me-P-Me-P-Me) binds not only five times stronger to a 229 base pair DNA fragment than d((TTTTTCTCTCTCTCT)-C-Me-C-Me-C-Me-C-Me-C-Me) but also with higher selectivity; UV-melting experiments show that duplexes of d(TTTTTCTXTCTCTCT) (where X = P, P-Me, or P-OMe) With their antiparallel Watson-Crick complement are dramatically less stable (Delta T-m < -12 degrees C) at pH 8.0 than the corresponding natural duplex. Thus the new bases P and P-Me show Hoogsteen specific pairing behavior.