Ethyl 4-[(4-amino-1-methylpyrrole-2-carbonyl)amino]butanoate | 297731-23-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Ethyl 4-[(4-amino-1-methylpyrrole-2-carbonyl)amino]butanoate
• CAS: 297731-23-8
• 化学式: C₁₂H₁₉N₃O₃
• 分子量: 253.301
• InChiKey: YTOVEBRGVFXEPU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  86.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Ethyl 4-[(4-amino-1-methylpyrrole-2-carbonyl)amino]butanoate 在 4-二甲氨基吡啶 、 sodium hydroxide 、 碳酸二异丙酯 、 1-羟基苯并三唑 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.02h， 生成 Acetic acid (2R,3R,4S,5S,6R)-4,5-diacetoxy-6-acetoxymethyl-2-({4-[4-({4-[(1H-indole-2-carbonyl)-amino]-1-methyl-1H-pyrrole-2-carbonyl}-amino)-butyrylamino]-1-methyl-1H-pyrrole-2-carbonyl}-amino)-tetrahydro-pyran-3-yl ester
  参考文献：
  名称：

  Carbohydrate-Based DNA Ligands:  Sugar−Oligoamides as a Tool to Study Carbohydrate−Nucleic Acid Interactions

  摘要：

  Sugar-oligoamides have been designed and synthesized as structurally simple carbohydrate-based ligands to study carbohydrate-DNA interactions. The general design of the ligands 1-3 has been done as to favor the bound conformation of Distamycin-type gamma-linked covalent dimers which is a hairpin conformation. Indeed, NMR analysis of the sugar-oligoamides in the free state has indicated the presence of a percentage of a hairpin conformation in aqueous solution. The DNA binding activity of compounds 1-3 was confirmed by calf thymus DNA (ct-DNA) NMR titration. Interestingly, the binding of the different sugar-oligoamides seems to be modulated by the sugar configuration. Semiquantitative structural information about the DNA ligand complexes has been derived from NMR data. A competition experiment with Netropsin suggested that the sugar-oligoamide 3 bind to DNA in the minor groove. The NMR titrations of 1-3 with poly(dA-dT) and poly(dG-dC) suggested preferential binding to the ATAT sequence. TR-NOE NMR experiments for the sugar-oligoamide 3-ct-DNA complex both in D2O and H2O have confirmed the complex formation and given information on the conformation of the ligand in the bound state. The data confirmed that the sugar-oligoamide ligand is a hairpin in the bound state. Even more relevant to our goal, structural information on the conformation around the N-glycosidic linkage has been accessed. Thus, the sugar asymmetric centers pointing to the NH-amide and N-methyl rims of the molecule have been characterized.

  DOI：

  10.1021/ja050794n
• 作为产物：
  描述：

  2,2,2-三氯-1-(1-甲基-1H-吡咯-2-基)-乙酮 在 sodium tetrahydroborate 、 5%-palladium/activated carbon 、 硝酸 、 乙酸酐 、 三乙胺 作用下， 以 乙醇 、 水 、 乙酸乙酯 、 异丙醇 为溶剂， 反应 4.0h， 生成 Ethyl 4-[(4-amino-1-methylpyrrole-2-carbonyl)amino]butanoate
  参考文献：
  名称：

  糖寡酰胺：DNA小沟结合剂的合成

  摘要：

  糖寡酰胺已被设计和合成为结构简单的基于碳水化合物的配体，用于研究碳水化合物与小沟之间的DNA相互作用。在这里，我们报告了一种有效的溶液相合成策略，以获得两个广泛的糖寡酰胺家族。第一种，结构载体A（-Py [Me]-γ-Py-Ind），具有作为取代基存在于吡咯B的氮上的甲基，其连接至寡酰胺片段的C端。第二类，结构向量B（-Py [（CH 2）11OH]-γ-Py-Ind），在吡咯B的氮原子上存在一个烷基链，连接至寡酰胺片段的C末端，并且设计成可接触二价和多价的糖寡酰胺。通过使用顺序的DIPC / HOBt偶联反应，已构建了寡酰胺片段-Py [R]-γ-Py-Ind。端基氨基糖和寡酰胺片段之间的最后偶联反应是通过活化酸衍生物作为BtO-酯来进行的，这是使用TFFH进行的。使用DMF中的DIEA将分离的酯（BtO-Py [R]-γ-Py-Ind）与选定的氨基糖偶联。合成两种不同的选择性模型载体（

  DOI：

  10.1021/jo302238u

文献信息

• Synthesis of DNA-Sequence-Selective Hairpin Polyamide Platinum Complexes
  作者：Robin I. Taleb、David Jaramillo、Nial J. Wheate、Janice R. Aldrich-Wright

  DOI：10.1002/chem.200601486

  日期：2007.4.5

  DNA-sequence-selective hairpin polyamide platinum(II) complexes, containing pyrrole and imidazole heterocyclic rings, have been synthesised by different methods. A six-ring complex, selective for (A/T)GGG(A/T) DNA sequences, was made by using solid-phase synthesis, whilst an eight-ring complex, selective for (A/T)CCTG(A/T) DNA sequences, was made by utilising standard wet chemistry. Solid-phase synthesis resulted

  已通过不同方法合成了两种含有吡咯和咪唑杂环的DNA序列选择性发夹式聚酰胺铂（II）复合物。通过固相合成制备了对（A / T）GGG（A / T）DNA序列具有选择性的六环复合物，而对（A / T）CCTG（A / T）具有选择性的八环复合物DNA序列是通过使用标准的湿化学法制得的。固相合成比湿法合成具有更高的收率，更少的纯化且更有效。因此，这是进行进一步工作的首选方法。金属配合物通过（1）H和（195）Pt NMR光谱法和ESI质谱法表征。这两种化合物为合成包含多个发夹和/或铂基的更复杂分子提供了基础。
• Sugar–Oligoamides: Bound-State Conformation and DNA Minor-Groove-Binding Description by TR-NOESY and Differential-Frequency Saturation-Transfer-Difference Experiments
  作者：Florence Souard、Eva Muñoz、Pablo Peñalver、Concepción Badía、Rafael del Villar-Guerra、Juan Luis Asensio、Jesús Jiménez-Barbero、Cristina Vicent

  DOI：10.1002/chem.200701103

  日期：2008.3.7

  Selective-frequency saturation-transfer-difference (STD) spectra allow the description of complexes established between minor-groove binders and long tracts of calf thymus DNA (ct-DNA). Two sets of experiments with selective saturation of either the H1' or H4'/H5'/H5'' proton NMR regions of deoxyribose allow the description of the ligand residues close to the inner (H1') and outer regions (H4'/H5'/H5'')

  选择性频率饱和转移差异（STD）光谱可以描述在小沟结合物和小牛胸腺DNA（ct-DNA）的长片段之间建立的复合物。通过对脱氧核糖的H1'或H4'/ H5'/ H5''质子NMR区域进行选择性饱和的两组实验，可以描述靠近内部区域（H1'）和外部区域（H4'/ H5）的配体残基'/ H5''）双螺旋DNA的小沟。TR-NOESY和STD实验都研究了一系列糖寡核苷酸（2-6）与ct-DNA的配合物。配合物的结合模式类似于netropsin（1），使我们能够为该配体家族定义一般的结合模式，其中NH边缘指向DNA的小沟的内部区域（内部区域），CH3边缘指向DNA的小沟的外部部分（外部区域）。同样通过TR-NOESY和STD实验，已经获得了糖残基的不对称中心靠近凹槽的内部和外部的描述。这些结果证实糖是造成先前在结合能学中发现的差异的原因。
• A Convenient Method for the Synthesis of DNA-Recognizing Polyamides in Solution
  作者：Junhua Xiao、Gu Yuan、Weiqiang Huang、Albert S. C. Chan、K.-L. Daniel Lee

  DOI：10.1021/jo000135n

  日期：2000.9.1

  A convenient method for the synthesis of polyamides containing N-methylpyrrole (Py) and N-methylimidazole (Im) in solution has been developed. Most of the building blocks have been prepared by a haloform reaction in a simple way that column chromatography can be avoided. By use of the DCC/HOBT coupling reaction, the building blocks prepared have been effectively connected to construct a variety of subchains and polyamides without employing amino protection and deprotection. By use of the present method, an eight-ring polyamide, PyPyPyPy gamma PyImImPy beta Dp (gamma is gamma-aminobutyric acid, beta is beta-alanine, Dp is N,N-dimethylpropyldiamine), has been synthesized by the coupling of two four-ring subchains in one step.
• Synthesis and biophysical studies of hairpin polyamides targeting the Brn-3b and GATA-3 transcriptional sites
  作者：Balaji Babu、Hilary Mackay、Abby Prast、Kristin Dittenhafer、Ryan Davis、Christopher Tronrud、Toni Rice、Sameer Chavda、Moses Lee

  DOI：10.1515/hc.2010.002

  日期：2010.1.1

  Hairpin polyamide analogs of distamycin A (1) were designed and synthesized to evaluate their ability to bind 5'-ATAGA-3' and 5'-AGATA-3' sequences which are important elements for controlling the function of the Brn-3b and GATA-3 transcriptional factors, respectively. The hairpin polyamides are composed of pyrrole and imidazole units linked together via a.-aminobutyrate (GABA) unit. Hairpins 2b (Py-Py-Im-gamma-Py-Py-Py) and 2c (Im-Py-Py-gamma-Py-Py-Py) were synthesized to target the respective Brn-3b and GATA-3 cognate sequences. Preliminary biophysical studies including thermal denaturation and circular dichroism were performed and the results ascertained the binding of hairpins 2a and 2b to their respective cognate DNA sequences.
• Synthesis and Photoinduced DNA Cleaving Activity of Hairpin Polyamide–Chlorobenzenesulfonyl Conjugate¶
  作者：Fei Li Tang、Gu Yuan、Jin Wang

  DOI：10.1562/0031-8655(2003)078<0175:sapdca>2.0.co;2

  日期：——

  A hairpin polyamide-chlorobenzenesulfonyl conjugate was synthesized in solution by a haloform reaction and the dicyclohexvlcarbodiimide/1-hydroxybenzotriazole (DCC/HOBT) coupling reaction. Its ability to cleave DNA was investigated with supercoiled DNA (pBluescript SK), and the DNA cleaving efficiency of chlorobenzenesulfonyl group was enhanced by the hairpin polyamide under UV irradiation (365 nm).