A schematic diagram of a general Nucleoside
What are Nucleosides?
Nucleosides consist of a nitrogenous base (purine or pyrimidine) linked to a pentose sugar (ribose or deoxyribose) via a β-glycosidic bond. They form the foundational units of nucleotides and nucleic acids (DNA/RNA). In commercial and research contexts, "nucleosides" also include synthetically modified analogs with alterations to the sugar (e.g., 2'-F, 2'-O-Me) or base moiety (e.g., halogenation, novel heterocycles), which are critical for advanced applications in drug development and molecular biology.
Synthesis and Production
Nucleosides are produced through controlled synthetic routes, with chemical glycosylation being the primary method. This process involves:
- Protecting sensitive functional groups on both the sugar and nucleobase to ensure correct reactivity.
- Coupling an activated sugar derivative with a protected nucleobase to form the glycosidic bond with high β-selectivity, often using specialized catalysts.
- Deprotecting the intermediate under specific conditions to yield the final nucleoside product.
Alternative methods include enzymatic transglycosylation for specific analogs and microbial fermentation for large-scale production of natural nucleosides like adenosine and guanosine.
Application in Synthesis
Nucleosides serve as essential intermediates in synthesizing more complex molecules:
- They are phosphorylated to produce nucleotides (NTPs/dNTPs) for use in biochemistry, sequencing, and PCR, as well as nucleotide analog drugs.
- As building blocks for phosphoramidites and solid supports, they enable automated synthesis of oligonucleotides for therapeutics (e.g., ASOs, siRNA, CRISPR guide RNAs) and diagnostics (e.g., primers, probes).
- Many nucleoside analogs function directly as active pharmaceutical ingredients (APIs) in antivirals (e.g., Remdesivir, AZT), anticancer agents (e.g., Gemcitabine), and antiparasitics, often by inhibiting polymerase enzymes or causing chain termination.
