Synthesis of 2',5'-Dideoxy-2-fluoroadenosine and 2',5'-Dideoxy-2,5'-difluoroadenosine: Potent P-Site Inhibitors of Adenylyl Cyclase

摘要

Glycosylation of 2-fluoroadenine with the appropriate protected thioglycoside derivatives, followed by deprotection and anomer separation, produced the α- and α-anomers of 2',5'-dideoxy-2-fluoroadenosine (1), 2',5'-dideoxy-2,5'-difluoroadenosine (2), and 2'-deoxy-2-fluoroadenosine (3). These were examined as P-site inhibitors of adenylyl cyclase. The presence of fluorine on the purine ring increased potency of inhibition, and the most potent compound, β-2',5'-dideoxy-2-fluoroadenosine (1b), was 3 times more potent than β-2',5'-dideoxyadenosine.