Synthesis and applications of cyclonucleosides: an update (2010–2023)

Abstract

Cyclonucleosides are a group of nucleoside derivatives which, in addition to the classical N-glycosidic bond, have an additional covalent bond (linker, bridge) in their structure, which connects the heterocyclic base and sugar ring. The majority of them have been discovered in the laboratory; however, few such compounds have also been found in natural sources, including metabolites of sponges or radical damage occurring in nucleic acids. Due to their structural properties—rigid, fixed conformation—they have found wide applications in medicinal chemistry and biochemistry as biocides as well as enzyme inhibitors and molecular probes. They have also found use as convenient synthetic tools for the preparation of new nucleoside analogues, enabling structural modifications of both the sugar ring and heterocyclic base. This review summarizes the recent progress in the synthesis of various purine and pyrimidine cyclonucleosides using diverse chemical approaches based on radical, “click”, metal-mediated, and other types of reactions. It also presents recent reports concerning possible applications in medicinal chemistry, as well as their applications as valuable key intermediates in the synthesis of sugar- and base-modified nucleoside analogues and heterocyclic compounds. Graphical abstract