Tautomerism of isoguanosine and solvent-induced keto-enol equilibrium

Abstract

Ultraviolet and infrared absorption spectroscopy, in aqueous and non-aqueous media, have been employed to study the tautomerism of 9-substituted isoguanines, including the nucleoside isoguanosine. With the aid of a series of model compounds, it was shown that 9-substituted isoguanines, and isoguanosine, in aqueous medium are predominantly in the form N (1) H, 2-keto-6-amino. In dioxane solution the tautomeric equilibrium is shifted in the direction of the enol form. The shift towards this form is accentuated for those analogues in which the exocyclic amino group is methylated. With the aid of N6,N6, 9-trimethylisoguanine, and 9-octyl analogue, the tautomeric constant was studied as a function of concentration, temperature, and solvent polarity, and the results applied to evaluate the tautomeric equilibria of 9-methylisoguanine and isoguanosine as a function of these variables. In general the enol form is favoured by a decrease in solvent polarity, by a decrease in concentration in dioxane, or an increase in temperature in chloroform solution. Syntheses are described for several N6 amino and methylamino derivatives of 2-methoxy-9-methylpurine, and 3-methyl-5-oxo-7,8-dihydroimidazo (2,1-i) purine, which served as an analogue of the unavailable 1,9-dimethylisoguanine.