Premium
Synthesis, Structural, and Conformational Analysis of 4′‐ C ‐Alkyl‐2′‐ O ‐Ethyl‐Uridine Modified Nucleosides
Author(s) -
Nikam Rahul R.,
Harikrishna S.,
Gore Kiran R.
Publication year - 2021
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.202001348
Subject(s) - chemistry , glycosidic bond , nucleoside , stereochemistry , uridine , oligonucleotide , nucleic acid , covalent bond , dna , organic chemistry , enzyme , biochemistry , rna , gene
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.