Synthesis and Antiviral Activity of 2′‐Modified L‐Nucleoside Analogues

Abstract Nucleoside analogues have been the foundation of antiviral therapy over the past few decades. D‐nucleosides with natural stereochemistry occupies the lion share of the marketed antiviral agents. However, much less effort have been put towards the development of L‐nucleosides as antiviral agents. Herein, our effort towards the synthesis of 2 ′ ‐substituted L‐nucleoside analogues is reported as an emerging class of antiviral agents. Biological activity of the synthesized L‐nucleosided was evaluated against two viruses of importance, tick‐borne encephalitis virus (TBEV) and Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) in adenocarcinomic human alveolar basal epithelial cells (A459) and Vero cells. Ring opening of L‐2, 2′‐Anhydrouridine (2) with various nucleophiles to make several 2‘‐substituted L‐nucleosides is the key synthetic outcome. This development has paved the way in the synthesis of many new analogues of 2‘‐substituted L‐nucleosides for numerous applications.