Acetic acid (2R,3R,4R,5R)-4-acetoxy-5-acetoxymethyl-2-(3-oxo-5-[1,2,4]triazol-1-yl-3H-[1,2,4]triazin-2-yl)-tetrahydro-furan-3-yl ester | 257297-86-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: Acetic acid (2R,3R,4R,5R)-4-acetoxy-5-acetoxymethyl-2-(3-oxo-5-[1,2,4]triazol-1-yl-3H-[1,2,4]triazin-2-yl)-tetrahydro-furan-3-yl ester
• 英文别名: [(2R,3R,4R,5R)-3,4-diacetyloxy-5-[3-oxo-5-(1,2,4-triazol-1-yl)-1,2,4-triazin-2-yl]oxolan-2-yl]methyl acetate
• CAS: 257297-86-2
• 化学式: C₁₆H₁₈N₆O₈
• 分子量: 422.354
• InChiKey: FWVZYDSZONDKBJ-NMFUWQPSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  164
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  Acetic acid (2R,3R,4R,5R)-4-acetoxy-5-acetoxymethyl-2-(3-oxo-5-[1,2,4]triazol-1-yl-3H-[1,2,4]triazin-2-yl)-tetrahydro-furan-3-yl ester 在 氯化铵 、 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 24.0h， 以226 mg的产率得到(2R,3R,4R,5R)-2-(acetoxymethyl)-5-(5-amino-3-oxo-1,2,4-triazin-2(3H)-yl)tetrahydrofuran-3,4-diyl diacetate
  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
• 作为产物：
  描述：

  6-氮杂尿苷 在 吡啶 、 4-二甲氨基吡啶 、 三乙胺 、 三氯氧磷 作用下， 以 乙腈 为溶剂， 反应 6.5h， 生成 Acetic acid (2R,3R,4R,5R)-4-acetoxy-5-acetoxymethyl-2-(3-oxo-5-[1,2,4]triazol-1-yl-3H-[1,2,4]triazin-2-yl)-tetrahydro-furan-3-yl ester
  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

• US7179905B2
  申请人：——

  公开号：US7179905B2

  公开（公告）日：2007-02-20