SUBSTITUENT REACTIVITY AND TAUTOMERISM OF ISOGUANOSINE AND RELATED NUCLEOSIDES

Abstract

The substituent reactivity and tautomerism of isoguanine nucleosides is studied. Benzoylation or tosylation of isoguanine nucleosides (pyridine, room temperature) yields the 2-benzoyl derivatives 7c, 11, and 12 or the 2-tosyl compounds 13 and 14. The isobutyrylation of the 6-amino group which did not occur under these conditions was induced in the presence of Me(3)SiCl. In the absence of Me(3)SiCl, the reactivity of isoguanine substituents decreases in the order from 2-oxo --> 5'-OH --> 3'-OH --> 6-NH2. From isoguanine nucleosides, the N-1-(2b), N-3-(17), N-6-(15a, b), and 2-O-alkylated (3b) derivatives were prepared. Their pK(a) values were determined and the UV and C-13-NMR spectra compared with regard to the alkylation position. Also the tautomeric forms of isoguanine nucleosides were determined UV-spectrophotometrically in aqueous and nonaqueous solution. Isoguanosine (1a), its 2'-deoxy analogue 1b as well as the N-6-methyl- and 8-substituted derivatives form lactam tautomers in aqueous solution, whereas the lactim form is present in dioxane.