Formation of 2 '-deoxyoxanosine from 2 '-deoxyguanosine and nitrous acid: mechanism and intermediates

The reaction mechanism for the formation of 2'-deoxyoxanosine from 2'-deoxy guanosine by nitrous acid was explored using methyl derivatives of guanosin e and an isolated intermediate of the reaction, When 2-methylguanosine was incubated with NaNO2 under acidic conditions, N-5-methyloxanosine and 1-met hylxanthosine were generated, whereas the same treatment of N-2,N-2-dimethy lguanosine generated no product, In a similar experiment without NO2-, part icipation of a Dimroth rearrangement was ruled out. In the guanosine-HNO2 r eaction system, an intermediate with a half-life of 5.6 min (pH 7.0, 20 deg rees C) was isolated and tentatively identified as a diazoate derivative of guanosine, The diazoate intermediate was converted into oxanosine and xant hosine at a molar ratio (oxanosine:xanthosine) of 0.26 at pH 7.0 and 20 deg rees C, The ratio was not affected by the incubation pH between 2 and 10, b ut increased linearly with temperature from 0.22 (0 degrees C) to 0.32 (50 degrees C), The addition of acetone also increased the ratio up to 0.85 (98 % acetone), Based on these results, a con-ceivable pathway for the formatio n of 2'-deoxyoxanosine from 2'-deoxyguanosine by HNO2 is proposed.