N²-Isobutyryl-O⁶-[2-(4-nitrophenylethyl)]guanine | 143325-60-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: N²-Isobutyryl-O⁶-[2-(4-nitrophenylethyl)]guanine
• 英文别名: N²-isobutyryl-O⁶-[2-(p-nitrophenyl)ethyl]guanine；N²-isobutyryl-O⁶-(2-p-nitrophenylethyl)guanine；2-N-isobutyryl-6-O-[2-(4-nitrophenyl)ethyl]guanine；2-methyl-N-[6-[2-(4-nitrophenyl)ethoxy]-7H-purin-2-yl]propanamide
• CAS: 143325-60-4
• 化学式: C₁₇H₁₈N₆O₄
• 分子量: 370.368
• InChiKey: PGEAISOESGGWCG-UHFFFAOYSA-N

物化性质

• 密度：
  1.47±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  139
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N²-Isobutyryl-O⁶-[2-(4-nitrophenylethyl)]guanine 在 三氟甲磺酸三甲基硅酯 三甲基氯硅烷 、 N-甲基-N-(三甲基硅烷基)三氟乙酰胺 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 吡啶 为溶剂， 反应 44.0h， 生成 Benzoic acid 2-[(2R,3R)-3-acetoxymethyl-5-(2-isobutyrylamino-6-oxo-1,6-dihydro-purin-9-yl)-tetrahydro-furan-2-yl]-ethyl ester
  参考文献：
  名称：

  鸟苷类似物的高效区域选择性合成

  摘要：

  提出了允许在Vorbrüggen条件下将鸟嘌呤区域选择性引入鸟嘌呤（N 9对N 7）的反应条件。使用条件，已经制备了一组N 2-保护的鸟苷，其中N 2-异丁酰基-O 6- [2-（对硝基苯基）乙基]鸟嘌呤（1）为亲核试剂。这种方法有助于解决鸟苷类似物的一个重要的合成问题。

  DOI：

  10.1016/s0040-4039(00)61000-6

文献信息

• Amino acids bearing nucleobases for the synthesis of novel peptide nucleic acids
  作者：Gordon Lowe、Tirayut Vilaivan

  DOI：10.1039/a603696a

  日期：——

  All of the four nucleobases found in DNA have been incorporated in their protected form into the 4-position of N-tert-butoxycarbonyl-L-proline methyl ester with cis-stereochemistry. An efficient route for the synthesis of N-tert-butoxycarbonyl-trans-4-hydroxy-D -proline methyl ester has been developed from which the enantiomers may be synthesized. In addition an efficient synthesis of N-tert-butoxycarbonyl-N-(2-hydroxyethyl)glyc ine methyl ester has been achieved and its hydroxy group replaced with protected nucleobases using the Mitsunobu reaction

  DNA中的所有四种核苷酸碱基均已以其保护形式整合到了N-叔丁氧羰基-L-脯氨酸甲酯的4-位，并保持顺式立体化学结构。从N-叔丁氧羰基-反式-4-羟基-D-脯氨酸甲酯的高效合成路线中，可以制备其对映体。此外，还实现了N-叔丁氧羰基-N-(2-羟乙基)甘氨酸甲酯的高效合成，并通过 Mitsunobu 反应将其羟基替换为保护的核苷酸碱基。
• Dipeptides bearing nucleobases for the synthesis of novel peptide nucleic acids
  作者：Gordon Lowe、Tirayut Vilaivan

  DOI：10.1039/a603699f

  日期：——

  Three stereoisomers (cis-L, trans-D and cis-D) of N-Fmoc-glycyl-4-(thymin-1-yl)proline and their pentafluorophenyl esters have been prepared for use in the synthesis of novel peptide nucleic acids. In addition, N-Fmoc-glycyl-4-(N6-benzoyladenin- 9-yl)proline, N-Fmoc-glycyl-4-(N4-benzoylcytosin -1-yl)proline and N-Fmoc-glycyl-4-(N2-isobutyrylguan in-9-yl)proline and their pentafluorophenyl esters of the cis-D series have been synthesized.

  已经制备了N-Fmoc-甘氨酰-4-(胸腺嘧啶-1-基)脯氨酸的三种立体异构体（顺式-L、反式-D和顺式-D）及其五氟苯酯，用于合成新型肽核酸。此外，还合成了N-Fmoc-甘氨酰-4-(N6-苯甲酰腺嘌呤-9-基)脯氨酸、N-Fmoc-甘氨酰-4-(N4-苯甲酰胞嘧啶-1-基)脯氨酸和N-Fmoc-甘氨酰-4-(N2-异丁酰鸟嘌呤-9-基)脯氨酸及其顺式-D系列五氟苯酯。
• Homopolymeric pyrrolidine-amide oligonucleotide mimics: Fmoc-synthesis and DNA/RNA binding properties
  作者：T. H. Samuel Tan、Roberta J. Worthington、Robin G. Pritchard、Jordi Morral、Jason Micklefield

  DOI：10.1039/b613384n

  日期：——

  By chemically modifying or replacing the backbone of oligonucleotides it is possible to modulate the DNA and RNA recognition properties and fine-tune the physiochemical properties of oligomers. This is important because it challenges our understanding of natural nucleic acid structural and recognition properties and can lead to nucleic acid mimics with a wide range of applications in nucleic acid targeting, analysis or diagnostics. In this paper we describe the solid phase synthesis of pyrrolidine-amide oligonucleotide mimics (POMs) using Fmoc-peptide chemistry. This required the synthesis of adeninyl, cytosinyl, thyminyl and guaninyl pyrrolidine monomers, with Fmoc- and standard acyl-protecting groups on the exocyclic amino groups and nucleobases respectively. These monomers were used to synthesise several thyminyl and adeninyl POM pentamers, with modest coupling efficiency. The pentamers were purified by RP-HPLC, characterised by mass spectrometry and their DNA and RNA binding properties were investigated using UV thermal denaturation/renaturation experiments. This revealed that all the pentamers exhibit strong affinity for complementary nucleic acids. The further evaluation of longer mixed-sequence POMs is described in a second accompanying paper (R. J. Worthington et al., Org. Biomol. Chem., 2006, DOI: 10.1039/b613386j).

  通过化学修饰或替换寡核苷酸的主链，可以调节其对DNA和RNA的识别特性，并精细调整寡聚物的物理化学性质。这一点之所以重要，是因为它挑战了我们对天然核酸结构和识别特性的理解，并可能导致开发出一系列在核酸靶向、分析或诊断方面有广泛应用的核酸类似物。本文描述了使用Fmoc肽化学的吡咯烷酰胺寡核苷酸类似物（POMs）的固相合成。这需要合成腺苷基、胞苷基、胸苷基和鸟苷基吡咯烷单体，吡咯烷环外氨基分别带有Fmoc保护基团和标准酰基保护基团。这些单体被用于合成数种胸苷基和腺苷基POM五聚体，其偶联效率一般。五聚体通过RP-HPLC进行纯化，通过质谱法进行表征，并使用紫外光热变性/复性实验研究其与DNA和RNA的结合特性。结果显示，所有五聚体都显示出对互补核酸的强烈亲和力。对更长的混合序列POMs的进一步评估在另一篇伴随论文中描述（R. J. Worthington等，Org. Biomol. Chem., 2006, DOI: 10.1039/b613386j）。
• Carbocyclic analogs of nucleosides via modified Mitsunobu reactions
  作者：Thomas F. Jenny、Nicoletta Previsani、Steven A. Benner

  DOI：10.1016/0040-4039(91)85031-y

  日期：1991.11

  A set of carbocyclic nucleoside analogs have been prepared using a novel modification of the Mitsunobu reaction. This approach helps solve an important synthetic problem in the preparation of carbocyclic analogs of nucleosides.

  使用Mitsunobu反应的新修饰已经制备了一组碳环核苷类似物。该方法有助于解决核苷碳环类似物制备中的重要合成问题。
• Synthesis of Purine- and Pyrimidine-Substituted Heptadienes. The Stereochemistry of Cyclization and Cyclopolymerization Products
  作者：Jui-Yi Tsai、Kamal Hani Bouhadir、Jing-Lan Zhou、Thomas R. Webb、Yahong Sun、Philip B. Shevlin

  DOI：10.1021/jo026379k

  日期：2003.2.1

  A series of 1,6-heptadienes, substituted in the 4 position with nucleic acid bases 1-6, have been synthesized via Mitsunobu condensations. Guanine, adenine, thymine, and uracil derivatives can be prepared directly by coupling the protected base with 1,6-heptadien-4-ol (7). However, coupling protected cytosine and 7 gives an O-alkylated product. Thus, the cytosine derivative must be prepared from the

  通过Mitsunobu缩合合成了在4位被核酸碱基1-6取代的一系列1，6-庚二烯。鸟嘌呤，腺嘌呤，胸腺嘧啶和尿嘧啶衍生物可通过将受保护的碱基与1,6-庚二烯-4-醇偶联而直接制备（7）。但是，偶合受保护的胞嘧啶和7可得到O-烷基化产物。因此，必须通过三唑由尿嘧啶取代的庚二烯制备胞嘧啶衍生物。CCl（4）和BrCCl（3）自由基向这些加合物的自由基加成进行了研究。在所有情况下，均获得了1：1和1：2的加合物。1：1加合物被鉴定为最初形成的5-hexen-1-yl自由基的环化产物。环化以立体定向方式进行，仅产生四种可能的非对映异构体之一。NMR研究表明，该产品中所有取代基均为顺式。在向尿嘧啶取代的庚二烯中添加CCl（4）的情况下，通过对分离的环化产物进行X射线结构测定，证实了这一结论。1-6与SO（2）的自由基引发的环共聚反应得到具有顺式连接的五元环的1：1共聚物。聚（2-SO（2））的二维N