Studies on the synthesis of 2-bromomethylimidazole nucleosides related to AICA-riboside [5-amino-1-(β-D-ribofuranosyl)imidazole-4-carboxamide]

The synthesis of 2-methyl- and 2-bromomethyl-imidazole nucleoside derivatives, related to AICA-riboside, is described. Ethyl N-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl) acetimidate and ethyl N-(2,3-O-isopropylidene-β-D-ribofuranosyl) acetimidate, obtained from 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosylamine and 2,3-O-isopropylidene-D-ribofuranosylamine respectively, reacted with ethyl α-amino-α-cyanoacetate and α-amino-α-cyanoacetamide to give ethyl 5-amino-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)- and ethyl 5-amino-1-(2,3-O-isopropylidene-β-D-ribofuranosyl)-2-methyl-imidazole-4-carboxylate (3) and (5) and 5-amino-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)- and 5-amino-1-(2,3-O-isopropylidene-β-D-ribofuranosyl)-2-methylimidazole-4-carboxamide (4) and (6), respectively. Treatment of 5-amino-2-methylimidazole glucosides (3) and (4) with Ac2O and H3PO4 as catalyst followed by reaction with N-bromosuccimide (NBS) gave 5-(N,N-diacetylamino)-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-2-bromomethylimidazole-4-carboxylate and the N-acetyl 4-carboxamide analogue, (18) and (17) respectively. Deisopropylidenation of the 5-amino-2-methylimidazole ribosides (5) and (6) followed by acetylation with Ac2O in the presence of 4-dimethylaminopyridine gave 5-(N,N-diacetylamino)-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-2-methylimidazole-4-carboxylate and -4-carboxamide (12) and (10). Treatment of (12) with NBS afforded ethyl 5-(N,N-diacetylamino)-1-(2,3,5-tri-O-acetyl-β-D-ribofuranoyl)-2-bromomethylimidazole-4-carboxylate (16). Structural assignments were made on the basis of 1H n.m.r. spectra.We thank Miss Emilia Bay for technical assistance. We also thank the Consejo Superior de Investigaciones Cientificas for a Post-doctoral and a Doctoral Fellowship (to R. H. and J. I. A. respectively) and the Comisión Asesora de Investigacion Cientifica y Técnica for financial support