Application of Metathesis in Synthesis of Nucleoside Analogs

Nucleoside analogs may participate and interfere in some way with DNA or RNA replication, transcription or reverse transcription in bacteria or virus, which made them potential antibacterial or antivirus drugs. Some natural nucleosides behave biologically active in vitro, however, instability to enzyme and poor selectivity in vivo restrict their application in medicinal field. Synthesis of chemically modified nucleosides and their derivatives as biologically active molecules has been an important topic in nucleic acid medicinal chemistry. Metathesis reaction, an inter- or intramolecular exchange reaction of alkylidene catalyzed by metal-carbene complex, makes the synthesis of nucleoside analogs go into a new stage, and becomes one of the main routes for the synthesis of nucleoside analogs. Driven by the discovery and improvement of metathesis catalysts, such as Schrock catalysts, Grubbs catalysts etc., olefin-metathesis reactions, especially olefin ring-closing metathesis (RCM) and cross-metathesis (CM) reactions, are widely used in constructing functionalized sugars (or pseudo sugars) in nucleoside analog structures or connecting two nucleosides to form nucleotide dimers or trimers. Application of olefin metathesis reaction in the synthesis of nucleoside analogs, including carbocyclic nucleosides, 2', 3'-dideoxynucleosides, acyclonucleosides, polycyclic nucleosides, and nucleoside or nucleotide dimers or trimers, is reviewed in this paper.