Synthesis of 2′-deoxyguanosine from 2′-deoxyadenosine via C2 nitration

Abstract

An efficient synthetic method has been developed for the synthesis of 2′-deoxyguanosine from the more commercially available 2′-deoxyadenosine via late-stage C2 nitration in 48.7% total yield by a 5-step synthetic procedure. Crucially, 2′-deoxyadenosine was fully protected by bennzoyl groups and then nitrated at C2 by tetrabutylammonium nitrate/trifluoroacetic anhydride. The resulting 2-NO2 moiety was converted into 2-NH2 by Ni-catalyzed hydrogenolysis. Finally, 2′-deoxyguanosine was obtained from the diaminopurine intermediate by deaminase-catalyzed reaction. Furthermore, the 2-NO2 moiety also appeared to be a versatile handle to introduce a variety of functional groups, resulting in a divergent access to 2-substituted 2′-deoxyadenosine analogues.