Fluorinated Nucleosides: Synthesis, Modulation in Conformation and Therapeutic Application

Abstract

Over the last twenty years, fluorination on nucleoside has established itself as the most promising tool to use to get biologically active compounds that could sustain the clinical trial by affecting the pharmacodynamics and pharmacokinetic properties. Due to fluorine's inherent unique properties and its judicious introduction into the molecule, makes the corresponding nucleoside metabolically very stable, lipophilic, and opens a new site of intermolecular binding. Fluorination on various nucleosides has been extensively studied as a result, a series of fluorinated nucleosides come up for different therapeutic uses which are either approved by the FDA or under the advanced stage of the clinical trial. Here in this review, we are summarizing the latest development in the chemistry of fluorination on nucleoside that led to varieties of new analogs like carbocyclic, acyclic, and conformationally biased nucleoside and their biological properties, the influence of fluorine on conformation, oligonucleotide stability, and their use in therapeutics.

4′-Fluoro-nucleosides and nucleotides: from nucleocidin to an emerging class of therapeutics

“…In pharmaceuticals research, nucleosides modified by selective fluorination on the ribose ring have proven to be a rich source of bioactives and a diversity of such compounds has been developed for a variety of applications, most prominently as antiviral agents. 21–24 Significant compounds of this class are illustrated in Fig. 2.…”

N‐Fluoroalkylated Morpholinos – a New Class of Nucleoside Analogues

“…[7,8] Therefore, fluorination of bioactive molecules, including nucleosides, is an important strategy in the design and discovery of novel drug candidates. [9,10] Currently, many fluorinated nucleoside analogues, for example 5-fluoro-2'-deoxyuridine, gemcitabine, trifluorothymidine, emtricitabine, fludarabine, capecitabine, clofarabine, are approved for the treatment of viral infections and cancer, [11,12] moreover, 2'-deoxy-2'-fluorinated ribonucleosides are common building blocks of small interfering RNA-based gene silencing drugs. [4,12] However, to the best of our knowledge, fluorine-containing morpholino derivatives have not yet been produced.…”

The Synthesis and Glycoside Formation of Polyfluorinated Carbohydrates

“…While the synthesis of polyfluorinated nucleosides is included, nucleoside formation of polyfluorinated sugar donors is not exhaustively covered. Reviews discussing fluorinated nucleosides are available. − …”