Synthesis of nucleosides

Synthesis of nucleosides involves the coupling of a nucleophilic, heterocyclic base with an electrophilic sugar. The silyl-Hilbert-Johnson (or Vorbrüggen) reaction, which employs silylated heterocyclic bases and electrophilic sugar derivatives in the presence of a Lewis acid, is the most common method for forming nucleosides in this manner. Synthesis of nucleosides involves the coupling of a nucleophilic, heterocyclic base with an electrophilic sugar. The silyl-Hilbert-Johnson (or Vorbrüggen) reaction, which employs silylated heterocyclic bases and electrophilic sugar derivatives in the presence of a Lewis acid, is the most common method for forming nucleosides in this manner. Nucleosides are typically synthesized through the coupling of a nucleophilic pyrimidine, purine, or other basic heterocycle with a derivative of ribose or deoxyribose that is electrophilic at the anomeric carbon. When an acyl-protected ribose is employed, selective formation of the β-nucleoside (possessing the S configuration at the anomeric carbon) results from neighboring group participation. Stereoselective synthesis of deoxyribonucleosides directly from deoxyribose derivatives is more difficult to achieve because neighboring group participation cannot take place. Three general methods have been used to synthesize nucleosides from nucleophilic bases and electrophilic sugars. The fusion method involves heating the base and acetyl-protected 1-acetoxyribose to 155 °C and results in the formation of the nucleoside with a maximum yield of 70%.