3’-(9-fluorenylmethoxycarbonyl)amino-2’,3’-dideoxyadenosine | 1418009-27-4

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 3’-(9-fluorenylmethoxycarbonyl)amino-2’,3’-dideoxyadenosine
• CAS: 1418009-27-4
• 化学式: C₂₅H₂₄N₆O₄
• 分子量: 472.503
• InChiKey: XHFFEYMBHLSDHL-PWRODBHTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  35.0
• 可旋转键数：
  5.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  137.41
• 氢给体数：
  3.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  3’-(9-fluorenylmethoxycarbonyl)amino-2’,3’-dideoxyadenosine 在 哌啶 、 磷酸三甲酯 、 1,8-双二甲氨基萘 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.67h， 生成 3’-amino-2’,3’-dideoxyadenosine-5’-phosphorimidazolide
  参考文献：
  名称：

  Synthesis of N3′-P5′-linked Phosphoramidate DNA by Nonenzymatic Template-Directed Primer Extension

  摘要：

  A fast and accurate pathway for nonenzymatic RNA replication would simplify models for the emergence of the RNA world from the prebiotic chemistry of the early earth. However, numerous difficulties stand in the way of an experimental demonstration of effective nonenzymatic RNA replication. To gain insight into the necessary properties of potentially self-replicating informational polymers, we have studied several model systems based on amino-sugar nucleotides. Here we describe the synthesis of N3'-P5'-linked phosphoramidate DNA (3'-NP-DNA) by the template-directed polymerization of activated 3'-amino-2',3'-dideoxyribonucleotides. 3'-NP-DNA is an interesting model because of its very RNA-like A-type duplex conformation and because activated 3'-amino-2',3'-dideozyribonucleotides are much more reactive than the corresponding activated ribonucleotides. In contrast to our previous studies with 2'-amino-2',3'-dideoxyribonucleotides (for which G and C but not A and T exhibit efficient template copying), we have found that all four canonical 3'-amino-2',3'-dideoxyribonucleotides (G, C, A, and T) polymerize efficiently on RNA templates. RNA templates are generally superior to DNA templates, and oligo-ribo-T templates are superior to oligo-ribo-U templates, which are the least efficient of the RNA homopolymer templates. We have also found that activation of 3'-aminonucleotides with 2-methylimidazole results in a ca. 10-fold higher polymerization rate relative to activation with imidazole, an observation that parallels earlier findings with ribonucleotides. We discuss the implications of our experiments for the possibility of self-replication in the 3'-NP-DNA and RNA systems.

  DOI：

  10.1021/ja311164j
• 作为产物：
  描述：

  3'-氨基-2',3'-双脱氧腺苷 、 9-芴甲基-N-琥珀酰亚胺基碳酸酯 在 吡啶 、 sodium carbonate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 3’-(9-fluorenylmethoxycarbonyl)amino-2’,3’-dideoxyadenosine
  参考文献：
  名称：

  Synthesis of N3′-P5′-linked Phosphoramidate DNA by Nonenzymatic Template-Directed Primer Extension

  摘要：

  A fast and accurate pathway for nonenzymatic RNA replication would simplify models for the emergence of the RNA world from the prebiotic chemistry of the early earth. However, numerous difficulties stand in the way of an experimental demonstration of effective nonenzymatic RNA replication. To gain insight into the necessary properties of potentially self-replicating informational polymers, we have studied several model systems based on amino-sugar nucleotides. Here we describe the synthesis of N3'-P5'-linked phosphoramidate DNA (3'-NP-DNA) by the template-directed polymerization of activated 3'-amino-2',3'-dideoxyribonucleotides. 3'-NP-DNA is an interesting model because of its very RNA-like A-type duplex conformation and because activated 3'-amino-2',3'-dideozyribonucleotides are much more reactive than the corresponding activated ribonucleotides. In contrast to our previous studies with 2'-amino-2',3'-dideoxyribonucleotides (for which G and C but not A and T exhibit efficient template copying), we have found that all four canonical 3'-amino-2',3'-dideoxyribonucleotides (G, C, A, and T) polymerize efficiently on RNA templates. RNA templates are generally superior to DNA templates, and oligo-ribo-T templates are superior to oligo-ribo-U templates, which are the least efficient of the RNA homopolymer templates. We have also found that activation of 3'-aminonucleotides with 2-methylimidazole results in a ca. 10-fold higher polymerization rate relative to activation with imidazole, an observation that parallels earlier findings with ribonucleotides. We discuss the implications of our experiments for the possibility of self-replication in the 3'-NP-DNA and RNA systems.

  DOI：

  10.1021/ja311164j

文献信息

• Nonenzymatic Template-Directed Synthesis of Mixed-Sequence 3′-NP-DNA up to 25 Nucleotides Long Inside Model Protocells
  作者：Derek K. O’Flaherty、Lijun Zhou、Jack W. Szostak

  DOI：10.1021/jacs.9b04858

  日期：2019.7.3

  direct the synthesis of a complementary strand composed of N3′→P5′ phosphoramidate DNA (3′-NP-DNA) using 3′-amino-2′,3′-dideoxyribonucleotides activated with 2-aminoimidazole. Using only the four canonical nucleobases (A, G, C, and T) of modern DNA, we demonstrate the chemical copying of a variety of mixed-sequence RNA templates, both in solution and within model protocells, into complementary 3′-NP-DNA

  以非酶促方式有效地复制混合序列寡核苷酸模板是一个长期存在的问题，无论是在生命起源方面，还是在合成人工生命系统的自下而上的努力方面。在这里，我们报告了一种高效且序列通用的非酶促过程，其中 RNA 模板使用 3'-amino-2',3' 指导合成由 N3'→P5' 氨基磷酸酯 DNA（3'-NP-DNA）组成的互补链-双脱氧核糖核苷酸被 2-氨基咪唑激活。仅使用现代 DNA 的四种经典核碱基（A、G、C 和 T），我们证明了将溶液中和模型原始细胞内的各种混合序列 RNA 模板化学复制到互补的 3'-NP- DNA 链。长达 25 个核苷酸的模板被化学转录，平均逐步产率为 96-97%。