Purines, pyrimidines, and imidazoles. Part 46. Some acyclic D-arabinose imidazole and purine nucleosides

Abstract

The reaction of D-arabinopyranosylamine with acetone, 2,2-dimethoxypropane, and toluene-p-sulphonic acid gave 3,4-O-isopropylidene-D-arabinopyranosylamine as a crystalline toluene-p-sulphonate, which with ethyl N-(α-cyano-β-ethoxyacryloyl)-N-methylcarbamate gave 1-α- and -β-D-arabinopyranosyl-5-cyano-3-methyluracils and with ethyl N-(carbamoylcyanomethyl)formimidate, after removal of the isopropylidene groups, 5-amino-1-α- and -β-D-arabinopyranosylimidazole-4-carboxamides. D-Ribopyranosylamine with dimethylformamide dimethyl acetal produced NN-dimethyl-N′-D-ribopyranosylformamidine; when this was heated with methanolic acetic acid and the product condensed with α-amino-α-cyanoacetamide, 5-amino-1-α-D-ribofuranosylimidazole-4-carboxamide and 5-amino-1-α- and -β-D-ribopyranosylimidazole-4-carboxamides were obtained, the structures of which were confirmed by conversion into the respective ribosylhypoxanthines by reaction with ethyl formate and sodium methoxide. D-Arabinopyranosylamine with dimethylformamide dimethyl acetal gave N-D-arabinopyranosyl-N′N′-dimethylformamidine; treatment of this with methanolic acetic acid followed by condensation with α-amino-α-cyanoacetamide produced 5-amino-1-α- and -β-D-arabinopyranosylimidazole-4-carboxamides, which were converted into the corresponding arabinosylhypoxanthines and 1 -(5-amino-4-carbamoylimidazol-1-yl)-1-O-methyl-D-arabinitol. The acyclic imidazolylarabinitol was converted by ethyl formate and sodium methoxide into 1-(hypoxanthin-9-yl)-1-O-methyl-D-arabinitol, which after acetylation, thiation with phosphorus pentasulphide, and deacylation produced 1-(6-mercaptohypoxanthin-9-yl)-1-O-methyl-D-arabinitol; this gave 1-(adenin-9-yl)-1-O-methyl-D-arabinitol by reaction with chlorine followed by ammonia.

Structures of the nucleosides were confirmed by periodate titration and u.v., mass, c.d., and ¹H n.m.r. spectroscopy, and a mechanism for the formation of the acyclic nucleosides is proposed.