1,4-bis[methyl-N,N'-4-[(tert-butoxycarbonyl)amino]pyrrolyl-2-carboxylate]-(E)-2-butene | 210298-49-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 1,4-bis[methyl-N,N'-4-[(tert-butoxycarbonyl)amino]pyrrolyl-2-carboxylate]-(E)-2-butene
• CAS: 210298-49-0
• 化学式: C₂₆H₃₆N₄O₈
• 分子量: 532.594
• InChiKey: RAKKIEZSSMKOIO-MDZDMXLPSA-N

物化性质

• 沸点：
  600.618±55.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.201±0.14 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.81
• 重原子数：
  38.0
• 可旋转键数：
  8.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  139.12
• 氢给体数：
  2.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  1,4-bis[methyl-N,N'-4-[(tert-butoxycarbonyl)amino]pyrrolyl-2-carboxylate]-(E)-2-butene 在 palladium on activated charcoal 氢气 作用下， 以 乙酸乙酯 为溶剂， 反应 2.0h， 以92%的产率得到1,4-bis[methyl-N,N'-4-[(tert-butoxycarbonyl)amino]pyrrolyl-2-carboxylate]butane
  参考文献：
  名称：

  A Comparison of H-Pin and Hairpin Polyamide Motifs for the Recognition of the Minor Groove of DNA

  摘要：

  In order to compare strategies for covalent linkage of pyrrole-imidazole (Py-Im) polyamide subunits, equilibrium association constants (K-a) were determined for a series of polyamides coupled either C-N with a gamma-aminobutyric acid linker (hairpin motif) or linked across a central Py/Py pair through a tetramethylene spacer (H-pin motif). Compared to the well-characterized hairpin motif, the H-pin motif represents a unique and relatively unexplored approach for increasing the affinity and the specificity of 2:1 polyamide-DNA complexes. Three H-pin polyamides containing six or 10 aromatic amino acid residues were synthesized by solid-phase methods using a Boc-protected bispyrrole monomer combined with bi-directional synthesis. The DNA-binding properties of six-ring and 10-ring H-pin polyamides were analyzed by quantitative DNase I footprint titration on a DNA fragment containing five or seven base pair match and mismatch sequences, respectively. The homodimeric H-Pin (ImPyPy-beta-Dp)(2)C-4 (site of the tetramethylene linker indicated in bold type) binds to the seven base pair match sequence 5'-TGTCA-3' with K-a = 9.3 x 10(6) M-1 and 9.4-fold specificity relative to the single base mismatch sequence 5'-TGT (T) under bar A-3' (K-a = 9.9 x 10(6) M-1). The heterodimeric H-Pin (ImPyPy-beta-Dp)C-4(AcPyPyPy-beta-Dp) binds a 5'-TGTTA-3' match sequence with K-a = 2.0 x 10(6) M-1 and 3.5-fold specificity versus the single base mismatch sequence 5'-TGT (C) under bar A-3' (K-a = 5.7 x 10(5) M-1). The 10-ring H-pin (ImPyPyPyPy-beta-Dp)(2)C-4 binds to the seven base pair match sequence 5'-TGTAACA-3' with K-a = 4.4 x 10(8) M-1 and 28-fold specificity versus the single base pair mismatch sequence 5'-TG (G) under bar AACA-3' (K-a = 1.6 x 10(7) M-1). We find that H-pin polyamides bind with four- to 180-fold enhanced affinity and two- to 10-fold enhanced specificity relative to unlinked analogues, but with 25- to 150-fold reduced affinity and approximately one- to 20-fold reduced specificity compared to the corresponding hairpin polyamides. These results indicate that H-pin polyamides represent a viable motif for the recognition of predetermined sequences in the DNA minor groove; however, DNA-binding properties appear inferior to the corresponding hairpins.

  DOI：

  10.1002/(sici)1521-3765(19980515)4:5<796::aid-chem796>3.0.co;2-g
• 作为产物：
  描述：

  methyl 4-amino-1H-pyrrole-2-carboxylate 在 palladium on activated charcoal 氢气 、 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 42.5h， 生成 1,4-bis[methyl-N,N'-4-[(tert-butoxycarbonyl)amino]pyrrolyl-2-carboxylate]-(E)-2-butene
  参考文献：
  名称：

  A Comparison of H-Pin and Hairpin Polyamide Motifs for the Recognition of the Minor Groove of DNA

  摘要：

  In order to compare strategies for covalent linkage of pyrrole-imidazole (Py-Im) polyamide subunits, equilibrium association constants (K-a) were determined for a series of polyamides coupled either C-N with a gamma-aminobutyric acid linker (hairpin motif) or linked across a central Py/Py pair through a tetramethylene spacer (H-pin motif). Compared to the well-characterized hairpin motif, the H-pin motif represents a unique and relatively unexplored approach for increasing the affinity and the specificity of 2:1 polyamide-DNA complexes. Three H-pin polyamides containing six or 10 aromatic amino acid residues were synthesized by solid-phase methods using a Boc-protected bispyrrole monomer combined with bi-directional synthesis. The DNA-binding properties of six-ring and 10-ring H-pin polyamides were analyzed by quantitative DNase I footprint titration on a DNA fragment containing five or seven base pair match and mismatch sequences, respectively. The homodimeric H-Pin (ImPyPy-beta-Dp)(2)C-4 (site of the tetramethylene linker indicated in bold type) binds to the seven base pair match sequence 5'-TGTCA-3' with K-a = 9.3 x 10(6) M-1 and 9.4-fold specificity relative to the single base mismatch sequence 5'-TGT (T) under bar A-3' (K-a = 9.9 x 10(6) M-1). The heterodimeric H-Pin (ImPyPy-beta-Dp)C-4(AcPyPyPy-beta-Dp) binds a 5'-TGTTA-3' match sequence with K-a = 2.0 x 10(6) M-1 and 3.5-fold specificity versus the single base mismatch sequence 5'-TGT (C) under bar A-3' (K-a = 5.7 x 10(5) M-1). The 10-ring H-pin (ImPyPyPyPy-beta-Dp)(2)C-4 binds to the seven base pair match sequence 5'-TGTAACA-3' with K-a = 4.4 x 10(8) M-1 and 28-fold specificity versus the single base pair mismatch sequence 5'-TG (G) under bar AACA-3' (K-a = 1.6 x 10(7) M-1). We find that H-pin polyamides bind with four- to 180-fold enhanced affinity and two- to 10-fold enhanced specificity relative to unlinked analogues, but with 25- to 150-fold reduced affinity and approximately one- to 20-fold reduced specificity compared to the corresponding hairpin polyamides. These results indicate that H-pin polyamides represent a viable motif for the recognition of predetermined sequences in the DNA minor groove; however, DNA-binding properties appear inferior to the corresponding hairpins.

  DOI：

  10.1002/(sici)1521-3765(19980515)4:5<796::aid-chem796>3.0.co;2-g