Synthesis of 8-[18O]hydroxy-2′-deoxyguanosine

8-[18O]Hydroxy-2′-deoxyguanosine was synthesized starting from 8-bromo-2′-deoxyguanosine and the sodium salt of [18O]benzyl alcohol, resulting in the intermediate 8-[18O]benzyloxy-2′-deoxyguanosine. Subsequent reduction by catalytic transfer hydrogenation, yielded the desired product 8-[18O]hydroxy-2′-deoxyguanosine. 8-Bromo-2′-deoxyguanosine was synthesized from 2′-deoxyguanosine by treatment with Br2. The sodium salt of [18O]benzyl alcohol was prepared by treatment of ethyl benzimidate hydrochloride with H218O (95%), LiAlH4 and sodium hydride. Starting from H218O the overall yield of 8-[18O]hydroxy-2′-deoxyguanosine was approximately 4%. The isotopic purity was calculated to be 93.4 atom% based on GC-MS measurements. The chemical purity and the isotopic purity comply with the planned application, namely as internal standard for the determination of 8-hydroxy-2′-deoxyguanosine by GC-MS.