SYNTHESIS OF 2-AMINOPURINE NUCLEOSIDES VIA REGIOCONTROLLED GLYCOSYLATION

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 N-9-beta-2-aminopurine nucleosides. Glycosylation of N2-acetyl-2-amino-6-chloropurine could be made to produce either N-9-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 N-9-nucleosides with either base. The 2-amino-6-chloropurine derivatives were converted to their corresponding 2-aminopurine nucleosides by hydrogenolysis (H-2, Pd/C). A convenient NOESY protocol for establishing base regiochemistry and anomeric stereochemistry is also presented.