Synthesis of Adenine Nucleosides with a Reactive (β-Iodovinyl)sulfone or (β-Keto)sulfone Group at the C2 Position and Their Polymerase-Catalyzed Incorporation into DNA.

Iodosulfonylation of an ethynyl group at the C2 position of 2'-deoxyadenosine or adenosine with TsI provides (E)-2-(β-iodovinyl)sulfones. The latter undergo nucleophilic substitution with amines via an addition-elimination to give β-sulfonylvinylamines (enamines). Acid-catalyzed hydrolysis of the β-sulfonylvinylamines provides 2-(β-keto)sulfones, mechanistically different probes that react with alkyl halides, resulting in α-alkylation. Adenine nucleosides with a β-ketosulfone group at C2, during conversion to their 5'-triphosphate form, undergo an unexpected conversion to 2-carboxylic acid nucleotides. The 5'-triphosphate of 2'-deoxyadenosine-2-carboxylic acid was incorporated by a human DNA polymerase into a one-nucleotide gap DNA substrate.