Characterization of 5-hydroxy-8-oxo-7,8-dihydroguanosine in the photosensitized oxidation of 8-oxo-7,8-dihydroguanosine and its rearrangement to spiroiminodihydantoin

The photosensitized oxidation of 2',3',5'-tris-(O-tert-butyldimethylsilyl)-8-oxo-7,8-dihydroguansine (8-oxoG) with singlet oxygen was studied by low-temperature NMR. A stable intermediate was characterized at -60 degreesC by C-13, 2D NMR HMBC spectra, and chemical shifts calculated by hybrid Hallree-Fock density functional theory which agreed with the structure 5-hydroperoxy-8-oxo-7,8-dihydroquanosine. Reduction of this intermediate at low temperature afforded the corresponding alcohol, the long-postulated 5-hydroxy8-oxo-7,8-dihydroguanosine, the last intermediate in the formation of spiroiminodihydantoin. Upon warming to room temperature, this alcohol rearranges to form the spiroiminodihydantoin in good yield within 2 h.