3-methyl-2-[(N-phenoxyacetyl)amino]-5-{5'-O-[(4,4'-dimethoxytriphenyl)methyl]-2'-deoxy-β-D-ribofuranosyl}pyridine | 190907-98-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 3-methyl-2-[(N-phenoxyacetyl)amino]-5-{5'-O-[(4,4'-dimethoxytriphenyl)methyl]-2'-deoxy-β-D-ribofuranosyl}pyridine
• CAS: 190907-98-3
• 化学式: C₄₀H₄₀N₂O₇
• 分子量: 660.767
• InChiKey: JBKFIMHAWFOSEH-HKIDPNTFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.62
• 重原子数：
  49.0
• 可旋转键数：
  13.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  108.37
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  2-氰乙基N,N-二异丙基氯亚磷酰胺 、 3-methyl-2-[(N-phenoxyacetyl)amino]-5-{5'-O-[(4,4'-dimethoxytriphenyl)methyl]-2'-deoxy-β-D-ribofuranosyl}pyridine 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以81%的产率得到3-methyl-2-[N-(phenoxyacetyl)amino]-5-{5'-O-[(4,4'-dimethoxytriphenyl)methyl]-2'-deoxy-β-D-ribofuranosyl}pyridine-3'-O-(2-cyanoethyl-N,N-diisopropyl)phosphoramidite
  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：

  3-methyl-2-[(N-phenoxyacetyl)amino]-5-(β-D-ribofuranosyl)pyridine 在 偶氮二异丁腈 、 1,1,1,3,3,3-hexamethyltrisilane 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 吡啶 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 17.0h， 生成 3-methyl-2-[(N-phenoxyacetyl)amino]-5-{5'-O-[(4,4'-dimethoxytriphenyl)methyl]-2'-deoxy-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