61373-43-1Relevant academic research and scientific papers
Synthesis, Structural, and Conformational Analysis of 4′-C-Alkyl-2′-O-Ethyl-Uridine Modified Nucleosides
Nikam, Rahul R.,Harikrishna,Gore, Kiran R.
, p. 924 - 932 (2021)
Sugar modifications have attracted much attention due to their potential structural and functional influence on therapeutic nucleic acids. Herein, we report the synthesis of dual modified 4′-C-azidomethyl-2′-O-ethyl-uridine (4′-AzM-2′-OEt?U) and 4′-C-aminomethyl-2′-O-ethyl-uridine (4′-AM-2′-OEt?U) nucleosides using linear multi-step synthesis (16 linear steps). Additionally, we report an alternative route for the synthesis of 2′-O-ethyl-uridine nucleoside which has been achieved in three steps with an overall yield of 40 %. X-ray structure of 4′-AzM-2′-OEt?U illustrates that the nucleoside adopts C2′-endo (South) conformation having a DNA-type glycosidic bond (χ) angle of ?116.01°. Computational studies revealed the C2′-endo and C4′-exo conformations for 4′-AzM-2′-OEt?U and 4′-AM-2′-OEt?U free nucleosides, respectively. The C4′-exo conformation in 4′-AM-2′-OEt?U free nucleoside is collectively stabilized by various non-covalent interactions between positively charged aminomethyl and 2′,3′-hydroxyl groups. Insights into the structural and conformational analysis of dual sugar modified nucleosides and oligonucleotides will be helpful in the rational design of modified nucleosides and therapeutic oligonucleotides.
