Synthesis and PMR spectra of 7‐hydroxyalkylguanosinium acetates

Abstract

AbstractGuanosine and 9‐methylguanine treated with epoxides in glacial acetic acid are hydroxyalkylated stereoselectively at the N7 position of the guanine moiety. Previously unreported 7‐(hydroxyalkyl)guanosinium acetates from the reactions of six epoxides with guanosine and 7‐(hydroxyalkyl)‐9‐methylguaninium acetates from the reactions of two epoxides with 9‐methyl guanine in glacial acetic acid have been prepared and characterized by their pmr spectra. By using an excess of epoxide, quantitative conversion of guanosine or 9‐methylguanine to the corresponding 7‐hydroxyalkylguanosinium or 7‐hydroxyalkyl‐9‐methylguaninium acetate was achieved. Comparisons of the pmr spectra of the 7‐(hydroxyalkyl)guanosinium acetates in DMSO‐d6 to the spectrum of guanosine reveal that the H8 and amino group proton absorptions common to guanosine are shifted to a lower field, the absorptions of the H1 proton is absent, and the coupling constant of the H′1‐H′2 protons of the ribosyl group is decreased from about 5.7 ± 0.1 Hz in guanosine to about 3.5 ± 0.1 Hz in the products. The use of the pmr spectral features of 7‐(hydroxyalkyl)‐9‐methylguaninium compounds in characterizing 7‐hydroxyalkylguanosinium compounds is discussed. Evidence is presented which suggests that extensive delocalization of positive charge exists in both the pyrimidine and imidazole rings of N7‐hydroxyalkylated guanosine and N7‐hydroxyalkylated‐9‐methylguanine. The possible effects of charge delocalization upon the hydrogen bonding potential of 7‐hydroxyalkylated guanine moieties in DNA is discussed.