Department of Chemistry, Indian Institute of Technology Bombay , Mumbai 400076, India.
J Org Chem. 2013 Oct 4;78(19):9956-62. doi: 10.1021/jo4012333. Epub 2013 Sep 24.
Herein, we report the synthesis of 4'-C-aminomethyl-2'-deoxy-2'-fluorouridine, a therapeutically appealing RNA modification. Conformational analysis by DFT calculations and molecular dynamics simulations using trinucleotide model systems revealed that modified sugar adopts C3'-endo conformation. In this conformer, a weak intramolecular C-H···F H-bond between the hydrogen atom of the 4'-C-CH2 group and the F atom at the 2' position is observed. Comparative studies with unmodified, 2'-fluoro-, 2'-O-methyl-, and 4'-C-aminomethyl-2'-O-methyluridine showed the chemical nature of 2'-substituent dictates the sugar puckering of 2',4'-modified nucleotides.
在这里，我们报告了 4'-C-氨甲基-2'-脱氧-2'-氟尿苷的合成，这是一种有吸引力的治疗性 RNA 修饰物。使用三核苷酸模型系统通过 DFT 计算和分子动力学模拟进行的构象分析表明，修饰后的糖采用 C3'-endo 构象。在这种构象中，观察到 4'-C-CH2 基团的氢原子和 2'位的 F 原子之间的弱分子内 C-H···F H 键。与未修饰的、2'-氟代的、2'-O-甲基的和 4'-C-氨甲基-2'-O-甲基尿苷的比较研究表明，2'-取代基的化学性质决定了 2'，4'-修饰核苷酸的糖构象。
