N-2,3-ETHENO-2'-DEOXYGUANOSINE [8,9-DIHYDRO-9-OXO-2'-DEOXY-3-BETA-D-RIBOFURANOSYLIMIDAZO[2,1-B]PURINE] - A PRACTICAL SYNTHESIS AND CHARACTERIZATION

The literature methods for the syntheses of N2,3-etheno-2'-deoxyguanosine (1a) and its 5'-O-phosphate are associated with very low overall yields. We now describe a route starting in the riboside series that permits the production of 1a in practical quantities and has allowed its complete chemical characterization for the first time. O6-Benzylguanosine (6b) when treated with bromoacetaldehyde under conditions of continuous buffering gives the N2,3-etheno derivative 7b in 48% yield. The 3',5'-O-(1,1,3,3-tetraisopropyldisiloxa-1,3-diyl) derivative (8b, 89 % yield) of 7b when allowed to react with phenyl chlorothionoformate led to the corresponding 2' ester (10,50%). 2'-Deoxygenation of 10 by the Barton procedure then afforded 65% of 11, and deprotection of the latter (Bu4N+F-) gave 12 quantitatively. Catalytic hydrogenation of 12 then produced pure la in 86% yield. Stability studies on la have confirmed its exquisite sensitivity to acid and demonstrated its relative stability to alkali and the other reagents used in automated DNA synthesis (phosphoramidate method).