Synthesis of 2-chloro-2'-5'-dideoxy-5'-difluoromethylphosphinyladenosine: A nonhydrolyzable isosteric, isopolar analog of 2-chlorodeoxyadenosine monophosphate

Article abstract of DOI:10.1055/s-1996-4314

2-Chloro-2'-5'-dideoxy-5'-difluoromethylphosphinyladenosine (5) was synthesized in thirteen steps from 3-O-benzyl-1,2-O-isopropylidene-α-D-ribofuranoside (1), a carbohydrate which is substituted differently at the 2- and 3-positions, making possible selective deprotection and reductive deoxygenation at the 2'-position of a nucleoside subsequent to glycosylation. Purine nucleoside phosphonate 5 is an analog of the monophosphate ester of the potent, clinically effective immunomodulatory agent 2-chlorodeoxyadenosine (2-CdA), and was synthesized to present a potential means of circumventing drug resistance in target immune cells.