SYNTHESIS OF 2'-5'-DIDEOXY-5'-DIFLUOROMETHYLPHOSPHINYLADENOSINE - A NONHYDROLYZABLE ISOSTERIC, ISOPOLAR ANALOG OF 2-CHLORODEOXYADENOSINE MONOPHOSPHATE

2'-5'-dideoxy-5'-difluoromethylphosphinyladenosine (5) was synthesized in thirteen steps from benzyl-1,2-O-isopropylidene-alpha-D-ribofurano side (1), a carbohydrate which is substituted differently at the 2- an d 3-positions, making possible selective deprotection and reductive de oxygenation at the 2'-position of a nucleoside subsequent to glycosyla tion. Purine nucleoside phosphonate 5 is an analog of the monophosphat e ester of the potent, clinically effective immunomodulatory agent 2-c hlorodeoxyadenosine (2-CdA), and was synthesized to present a potentia l means of circumventing drug resistance in target immune cells.