Synthesis of pyrimidine nucleoside analogues

Abstract EN

The uracil and thymine nucleoside analogues (11) and (12) were obtained via reaction of diacetone glucose (1) with dimethyl sulphoxide and acetic anhydride to give diacetone glucose-3-ulose derivative (2).

Reaction of compound (2) with dimethylmalonate under PTC (Phase Transfer Catalyst) yielded the malonate compound (3), which was converted to the 3-C-nitromethyl-3-C-dimethylmalonyl derivative (4), upon treatment with nitromethane in presence of sodium methoxide.

The isopropylidene at 5, 6-position was removed with acetic acid followed by periodate oxidation and borohydride reduction to give the ribo derivative (6).

The 5-hydroxy group was protected with benzoyl group using benzoyl chloride to give the 5-benzoate derivative (7).

Treatment of compound (7) with mixture of acetic acid, acetic anhydride and few drops of sulfuric acid to gave the 1, 2-di-O-acetylated compound (8).

When compound (8) was allowed to react with silylated thymine and uracil, compounds (9) and (10) were obtained.

Deprotection of compounds (9) and (10) under basic condition yield the new pyrimidine nucleoside analogues (11) and (12).