1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-5-fluorocytosine | 53294-73-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-5-fluorocytosine
• 英文别名: 2',3',5'-Tri-O-benzoyl-5-fluorocytidine；O^2'_,O3'_,O5'-tribenzoyl-5-fluoro-cytidine；[(2R,3R,4R,5R)-5-(4-amino-5-fluoro-2-oxopyrimidin-1-yl)-3,4-dibenzoyloxyoxolan-2-yl]methyl benzoate
• CAS: 53294-73-8
• 化学式: C₃₀H₂₄FN₃O₈
• 分子量: 573.534
• InChiKey: SHIAQLKLVORQGR-PMHJDTQVSA-N

物化性质

• 沸点：
  702.3±70.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  42
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  147
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-5-fluorocytosine 在 氨 作用下， 以 甲醇 为溶剂， 以92%的产率得到5-氟胞嘧啶核苷
  参考文献：
  名称：

  鸟嘌呤 N1 亚氨基质子在 DNA 低聚物中自由基阳离子迁移和反应中的作用

  摘要：

  鸟嘌呤核碱基氧化成 DNA 寡聚体中的自由基阳离子导致 N1 亚氨基质子的酸度增加，这可能导致其自发转移到配对胞嘧啶的 N3。这种质子转移被怀疑在 DNA 中的长距离自由基阳离子跳跃中起重要作用，并且在自由基阳离子与 H2O 或 O2 的反应中起决定性的产物决定作用。我们制备并研究了 DNA 寡聚体，其中某些脱氧胞苷被 5-氟-2'-脱氧胞苷 (F5dC) 取代。F5C 的 pKa 被确定为比 dC 低 1.7 个单位，这导致鸟嘌呤自由基阳离子的质子转移在热力学上是不利的。通过对共价连接的蒽醌衍生物进行紫外线照射，DNA 的光引发单电子氧化引入了自由基阳离子，该阳离子在整个低聚物中跳跃并在 GG 步骤中被选择性捕获。F5dC 的引入不会影响电荷跳跃的效率，但它显着减少了 GG 位点的反应量，正如随后与甲酰胺嘧啶糖基化酶反应所揭示的那样。这些发现表明鸟嘌呤自由基阳离子 N1 质子向胞嘧啶的转

  DOI：

  10.1021/ja0573763
• 作为产物：
  描述：

  5-氟尿嘧啶核苷 在 4-二甲氨基吡啶 、 氯化铵 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 三氯氧磷 作用下， 以 吡啶 、 乙腈 为溶剂， 反应 33.5h， 生成 1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-5-fluorocytosine
  参考文献：
  名称：

  Biochemical Detection of Cytidine Protonation within RNA

  摘要：

  Perturbation of active site functional group pK(a)s is an important strategy employed by protein enzymes to achieve catalysis. There is increasing evidence to indicate that RNAs also utilize functional group pK(a) perturbation for folding and reactivity. one of the best candidates for a functionally relevant pK(a) perturbation is the N3 of C (pK(a) 4.2), which could be sufficiently raised to allow protonation near physiological pH. Here we report the synthesis and use of a series of alpha -phosphorothioate tagged cytidine analogues whose altered N3 pK(a)s make it possible to efficiently detect functionally relevant protonation events by nucleotide analogue interference mapping. 6-Azacytidine (n(6)C alphaS) and 5-fluorocytidine (f(5)C alphaS) both have enhanced acidity at the N3 position (pK(a) 2.6 and 2.3, respectively) but leave the hydrogen bonding face of C otherwise unaffected. In contrast, pseudoisocytidine (Psi iC alphaS) is a charge neutral analogue that mimics the hydrogen bonding character of protonated C. To test the utility of these analogues, we characterized the C300(+)-G97-C277 mutant form of the Tetrahymena group I intron, which is predicted to require C300 protonation for ribozyme folding and reactivity. At neutral to alkaline pHs, C300 was the only site of n(6)C alphaS and f(5)C alphaS interference within the intron, yet both interferences were rescued at acidic pH. Furthermore,Psi iC alphaS substitution at C300 resulted in enhanced activity at alkaline pHs, consistent with the presence of an N3 proton under the pH conditions studied. Interference mapping with these analogues provides an efficient and sensitive means to identify every site within an RNA where cytidine protonation is important for RNA function and may make it possible to identify C's that participate in general acid/base catalysis within ribozyme active sites.

  DOI：

  10.1021/ja001918t

文献信息

• A Simplified Method for the Synthesis of Pyrimidine Nucleosides
  作者：A. Matsuda、Y. Kurasawa、K. A. Watanabe

  DOI：10.1055/s-1981-29590

  日期：——
• US4104461A
  申请人：——

  公开号：US4104461A

  公开（公告）日：1978-08-01
• Biochemical Detection of Cytidine Protonation within RNA
  作者：Adegboyega K. Oyelere、Scott A. Strobel

  DOI：10.1021/ja001918t

  日期：2000.10.1

  Perturbation of active site functional group pK(a)s is an important strategy employed by protein enzymes to achieve catalysis. There is increasing evidence to indicate that RNAs also utilize functional group pK(a) perturbation for folding and reactivity. one of the best candidates for a functionally relevant pK(a) perturbation is the N3 of C (pK(a) 4.2), which could be sufficiently raised to allow protonation near physiological pH. Here we report the synthesis and use of a series of alpha -phosphorothioate tagged cytidine analogues whose altered N3 pK(a)s make it possible to efficiently detect functionally relevant protonation events by nucleotide analogue interference mapping. 6-Azacytidine (n(6)C alphaS) and 5-fluorocytidine (f(5)C alphaS) both have enhanced acidity at the N3 position (pK(a) 2.6 and 2.3, respectively) but leave the hydrogen bonding face of C otherwise unaffected. In contrast, pseudoisocytidine (Psi iC alphaS) is a charge neutral analogue that mimics the hydrogen bonding character of protonated C. To test the utility of these analogues, we characterized the C300(+)-G97-C277 mutant form of the Tetrahymena group I intron, which is predicted to require C300 protonation for ribozyme folding and reactivity. At neutral to alkaline pHs, C300 was the only site of n(6)C alphaS and f(5)C alphaS interference within the intron, yet both interferences were rescued at acidic pH. Furthermore,Psi iC alphaS substitution at C300 resulted in enhanced activity at alkaline pHs, consistent with the presence of an N3 proton under the pH conditions studied. Interference mapping with these analogues provides an efficient and sensitive means to identify every site within an RNA where cytidine protonation is important for RNA function and may make it possible to identify C's that participate in general acid/base catalysis within ribozyme active sites.
• Role of the Guanine N1 Imino Proton in the Migration and Reaction of Radical Cations in DNA Oligomers
  作者：Avik K. Ghosh、Gary B. Schuster

  DOI：10.1021/ja0573763

  日期：2006.4.5

  Oxidation of a guanine nucleobase to its radical cation in DNA oligomers causes an increase in the acidity of the N1 imino proton that may lead to its spontaneous transfer to N3 of the paired cytosine. This proton transfer is suspected of playing an important role in long-distance radical cation hopping in DNA and the decisive product-determining role in the reaction of the radical cation with H2O

  鸟嘌呤核碱基氧化成 DNA 寡聚体中的自由基阳离子导致 N1 亚氨基质子的酸度增加，这可能导致其自发转移到配对胞嘧啶的 N3。这种质子转移被怀疑在 DNA 中的长距离自由基阳离子跳跃中起重要作用，并且在自由基阳离子与 H2O 或 O2 的反应中起决定性的产物决定作用。我们制备并研究了 DNA 寡聚体，其中某些脱氧胞苷被 5-氟-2'-脱氧胞苷 (F5dC) 取代。F5C 的 pKa 被确定为比 dC 低 1.7 个单位，这导致鸟嘌呤自由基阳离子的质子转移在热力学上是不利的。通过对共价连接的蒽醌衍生物进行紫外线照射，DNA 的光引发单电子氧化引入了自由基阳离子，该阳离子在整个低聚物中跳跃并在 GG 步骤中被选择性捕获。F5dC 的引入不会影响电荷跳跃的效率，但它显着减少了 GG 位点的反应量，正如随后与甲酰胺嘧啶糖基化酶反应所揭示的那样。这些发现表明鸟嘌呤自由基阳离子 N1 质子向胞嘧啶的转