Purine Nucleosides with a Reactive (β‐Iodovinyl)sulfone or a (β‐Keto)sulfone Group at the C8 Position and Their Polymerase‐Catalyzed Incorporation into DNA

Abstract

Iodosulfonylation of an ethynyl group attached at C8‐position of 2′‐deoxyadenosine or 2′‐deoxyguanosine A with TsNa or TsNHNH2, as tosyl source, and I2 or KI, as iodide source, provided 8‐(1‐iodo‐2‐tosylvinyl) nucleosides B with (β‐iodovinyl)sulfone group tethered to C8 position of the purine ring. Treatment of B with ammonia followed by acid‐catalyzed hydrolysis of the intermediary β‐sulfonylvinylamines C gave 8‐(β‐keto)sulfones D. The iodovinylsulfone probes B undergo nucleophilic substitution of iodide with thiols or amines, via an addition‐elimination path, to provide vinyl thioethers or vinyl amines, respectively. The 8‐(β‐keto)sulfone probes D react with electrophiles such as alkyl bromides resulting in α‐alkylation. The 5′‐triphosphate of 2′‐deoxyadenosine analog of D was incorporated by a human DNA polymerase into a double‐stranded DNA oligonucleotide possessing a one‐nucleotide gap substrate.