(1S,3R,4S,7R)-7-[2-cyanoethoxy(diisopropylamino)phosphinoxy]-1-(4,4′-dimethoxytrityloxymethyl)-3-(5-ethynyluracil-1-yl)-2,5-dioxabicyclo[2.2.1]heptane | 1275611-39-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: (1S,3R,4S,7R)-7-[2-cyanoethoxy(diisopropylamino)phosphinoxy]-1-(4,4′-dimethoxytrityloxymethyl)-3-(5-ethynyluracil-1-yl)-2,5-dioxabicyclo[2.2.1]heptane
• 英文别名: 3-[[(1S,3R,4S,7R)-1-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-3-(5-ethynyl-2,4-dioxopyrimidin-1-yl)-2,5-dioxabicyclo[2.2.1]heptan-7-yl]oxy-[di(propan-2-yl)amino]phosphanyl]oxypropanenitrile
• CAS: 1275611-39-6
• 化学式: C₄₂H₄₇N₄O₉P
• 分子量: 782.83
• InChiKey: FXUXVNJYARGAIE-LUAJEMIUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  56
• 可旋转键数：
  18
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  141
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  (1S,3R,4S,7R)-7-benzyloxy-1-methanesulfonyloxymethyl-3-(uracil-1-yl)-2,5-dioxabicyclo[2.2.1]heptane 在 吡啶 、 copper(l) iodide 、 四(三苯基膦)钯 、 ammonium cerium (IV) nitrate 、 palladium on carbon 、 四丁基氟化铵 、 氨 、 碘 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 甲酸 、 二氯甲烷 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 114.83h， 生成 (1S,3R,4S,7R)-7-[2-cyanoethoxy(diisopropylamino)phosphinoxy]-1-(4,4′-dimethoxytrityloxymethyl)-3-(5-ethynyluracil-1-yl)-2,5-dioxabicyclo[2.2.1]heptane
  参考文献：
  名称：

  C5-Alkynyl-Functionalized α-L-LNA: Synthesis, Thermal Denaturation Experiments and Enzymatic Stability

  摘要：

  Major efforts are currently being devoted to improving the binding affinity, target specificity, and enzymatic stability of oligonucleotides used for nucleic acid targeting applications in molecular biology, biotechnology, and medicinal chemistry. One of the most popular strategies toward this end has been to introduce additional modifications to the sugar ring of affinity-inducing conformationally restricted nucleotide building blocks such as locked nucleic acid (LNA). In the preceding article in this issue, we introduced a different strategy toward this end, i.e., C5-functionalization of LNA uridines. In the present article, we extend this strategy to alpha-L-LNA: i.e., one of the most interesting diastereomers of LNA. alpha-L-LNA uridine monomers that are conjugated to small C5-alkynyl substituents induce significant improvements in target affinity, binding specificity, and enzymatic stability relative to conventional alpha-L-LNA. The results from the back-to-back articles therefore suggest that C5-functionalization of pyrimidines is a general and synthetically straightforward approach to modulate biophysical properties of oligonucleotides modified with LNA or other conformationally restricted monomers.

  DOI：

  10.1021/jo5006153

文献信息

• [EN] NUCLEOBASE-FUNCTIONALIZED CONFORMATIONALLY RESTRICTED NUCLEOTIDES AND OLIGONUCLEOTIDES FOR TARGETING NUCLEIC ACIDS<br/>[FR] NUCLÉOTIDES ET OLIGONUCLÉOTIDES À CONFORMATION RESTREINTE À FONCTIONNALITÉ NUCLÉOBASE POUR CIBLER DES ACIDES NUCLÉIQUES
  申请人：UNIV IDAHO

  公开号：WO2011032034A3

  公开（公告）日：2011-07-21
• C5-Alkynyl-Functionalized α-L-LNA: Synthesis, Thermal Denaturation Experiments and Enzymatic Stability
  作者：Pawan Kumar、Bharat Baral、Brooke A. Anderson、Dale C. Guenther、Michael E. Østergaard、Pawan K. Sharma、Patrick J. Hrdlicka

  DOI：10.1021/jo5006153

  日期：2014.6.6

  Major efforts are currently being devoted to improving the binding affinity, target specificity, and enzymatic stability of oligonucleotides used for nucleic acid targeting applications in molecular biology, biotechnology, and medicinal chemistry. One of the most popular strategies toward this end has been to introduce additional modifications to the sugar ring of affinity-inducing conformationally restricted nucleotide building blocks such as locked nucleic acid (LNA). In the preceding article in this issue, we introduced a different strategy toward this end, i.e., C5-functionalization of LNA uridines. In the present article, we extend this strategy to alpha-L-LNA: i.e., one of the most interesting diastereomers of LNA. alpha-L-LNA uridine monomers that are conjugated to small C5-alkynyl substituents induce significant improvements in target affinity, binding specificity, and enzymatic stability relative to conventional alpha-L-LNA. The results from the back-to-back articles therefore suggest that C5-functionalization of pyrimidines is a general and synthetically straightforward approach to modulate biophysical properties of oligonucleotides modified with LNA or other conformationally restricted monomers.