Synthesis of 2-aminopurine nucleosides via regiocontrolled glycosylation

Article abstract of DOI:10.1016/S0040-4020(01)80438-5

The stereo- and regiocontrolled synthesis of pyranosyl 2-aminopurine nucleosides is described. Coupling of bissilylated N²-acetyl-2-aminopurine with peracetylated glucopyranosides (SnCl₄, (CH₂Cl)₂-MeCN, reflux) afforded good yields of the corresponding N⁹-β-2-aminopurine nucleosides. Glycosylation of N²-acetyl-2-amino-6-chloropurine could be made to produce either N⁹-nucleosides (TMSOTf, (CH₂Cl)₂, reflux), or N⁷-nucleosides (SnCl₄/MeCN, room temperature) selectively. Application of Knapp's thioglycoside procedure (NIS + TfOH, (CH₂Cl)₂, room temperature) produced the N⁹-nucleosides with either base. The 2-amino-6-chloropurine derivatives were converted to their corresponding 2-aminopurine nucleosides by hydrogenolysis (H₂, Pd/C). A convenient NOESY protocol for establishing base regiochemistry and anomeric stereochemistry is also presented.