Fluorinated nucleosides and oligonucleotides are of specific interest as probes for studying nucleic acids interaction, structures, biological transformations, and its biomedical applications. Among various modifications of oligonucleotides, fluorination of preformed nucleoside and/or nucleotides have recently gained attention owing to the unique properties of fluorine atoms imparting medicinal properties with respect to the small size, electronegativity, lipophilicity, and ability for stereochemical control. This review deals with synthetic protocols for selective fluorination either at sugar or base moiety in a preformed nucleosides, nucleotides and nucleic acids using specific fluorinating reagents.

Installation of cyano (CN-) functionality onto nucleosides has always been a challenging task for chemists and catalytic protocols developed for simple aryl substrates in most cases have failed to replicate their success when applied to nucleobase or sugar moiety of nucleosides. Given the importance of the cyano and amide functionalities in nucleoside chemistry, we herein disclose an efficient Pd-catalyzed cyanation protocol specifically applied to iodo-nucleobases. Furthermore, the developed methodology of cyanation has been explored for synthesis of naturally occurring and bio-active nucleosides such as toyocamycin, sangivamycin and Mycalisine A precursor has been demonstrated.