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

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Abstract
The reaction mechanism for the formation of 2'-deoxy-oxanosine from 2'-deoxyguanosine by nitrous acid was explored using methyl derivatives of guanosine and an isolated intermediate of the reaction. When 1-methylguanosine was incubated with NaNO(2)under acidic conditions, N (5) -methyloxanosine and 1-methylxanthosine were generated, whereas the same treatment of N (2), N (2)-dimethylguanosine generated no product. In a similar experiment without NO(2)(-), participation of a Dimroth rearrangement was ruled out. In the guanosine-HNO(2)reaction system, an intermediate with a half-life of 5.6 min (pH 7.0, 20 degrees C) was isolated and tentatively identified as a diazoate derivative of guanosine. The diazoate intermediate was converted into oxanosine and xanthosine at a molar ratio (oxanosine:xanthosine) of 0.26 at pH 7.0 and 20 degrees C. The ratio was not affected by the incubation pH between 2 and 10, but 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 formation of 2'-deoxyoxanosine from 2'-deoxyguanosine by HNO(2)is proposed.