The β-halovinyl sulfones and β-keto sulfones are useful intermediates in organic and medicinal chemistry. We have synthesized the adenosine and 2'-deoxyadenosine analogues modified at C2 position with reactive β-iodovinyl sulfones (e.g., 1-4) and β-keto sulfones (e.g., 5-8) to explore their reactivity with nucleophiles and electrophiles. Thus, iodosulfonylation of silyl protected 2-ethynyl-2'-deoxyadenosine with TsI in presence of NaOAc in THF at rt gave protected 2-(1-iodo-2-tosylvinyl)-2'-deoxyadenosine 1 (85%). Adenosine modified with iodovinyl sulfone at C2 3 has been prepared similarly. Desilylation of 1 and 3 with NH4F in the presence of AcOH in MeOH at 60 oC gave 2-(1-iodo-2-tosylvinyl)-2'-deoxyadenosine 2 (85%) and 2-(1-iodo-2-tosylvinyl)-adenosine 4 (80%), respectively. Treatment of β-iodovinyl sulfones (1-4) with methanolic ammonia at rt followed by acid hydrolysis with AcOH of the intermediary aminovinyl sulfones provided corresponding β-keto sulfones (5-8) in high yields. Reactivity of β-iodovinyl sulfones with nucleophiles and β-keto sulfones with electrophiles as well as incorporation of the 5′-triphosphate of 2 or 6 into double-stranded DNA by human or Escherichia coli DNA-polymerase-catalyzed reactions will be discussed. Moreover, reactivity and conformation of these C2-modified nucleosides will be compared with analogous C8-modified adenine and guanine derivatives which we reported earlier.

C-2 Substituted adenine nucleosides: Synthesis, reactivity and conformational study

ACS Spring Meeting 2021

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