Synthesis of 4,6-diamino-5-(polyhydroxyalkylamido)pyrimidines: conformation of the sugar chain

Condensation of 4,5,6-triaminopyrimidine with ethyl glycolate, d-ribono-1,4-lactone, d-allono-1,4-lactone, d-glucono-1,5-lactone, and l-gulono-1,4-lactone led to the corresponding 4,6-diamino-5-(hydroxyalkylamido)pyrimidines (1a–e). The conformations in acidic aqueous solution of these acyclic carbohydrate derivatives were determined from the proton–proton NMR coupling constants at 300 MHz. The polyhydroxyalkyl chain of compounds 1b–e adopt sickle conformations in order to avoid the 1,3-parallel interactions between hydroxyl groups present in the planar zigzag conformer. Cyclization of 4,6-diamino-5-(hydroxyacetamido)pyrimidine (1a) afforded 8-(hydroxymethyl)adenine (2a), which was acetylated to give 2f. The 13C NMR spectra of compounds 1a–e and 2a and f are also reported.