Pyrimidine Nucleosides with a Reactive (β-Chlorovinyl)sulfone or (β-Keto)sulfone Group at the C5 Position, Their Reactions with Nucleophiles and Electrophiles, and Their Polymerase-Catalyzed Incorporation into DNA

• Published in: ACS omega Vol. 3; no. 4; pp. 4276 - 4288
• Main Authors: Suzol, Sazzad H, Howlader, A. Hasan, Wen, Zhiwei, Ren, Yaou, Laverde, Eduardo E, Garcia, Carol, Liu, Yuan, Wnuk, Stanislaw F
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 30-04-2018
• ISSN: 2470-1343; 2470-1343
• DOI: 10.1021/acsomega.8b00584

Transition-metal-catalyzed chlorosulfonylation of 5-ethynylpyrimidine nucleosides provided (E)-5-(β-chlorovinyl)­sulfones A, which undergo nucleophilic substitution with amines or thiols affording B. The treatment of vinyl sulfones A with ammonia followed by acid-catalyzed hydrolysis of the intermediary β-sulfonylvinylamines gave 5-(β-keto)­sulfones C. The latter reacts with electrophiles, yielding α-carbon-alkylated or -sulfanylated analogues D. The 5′-triphosphates of A and C were incorporated into double-stranded DNA, using open and one-nucleotide gap substrates, by human or Escherichia coli DNA-polymerase-catalyzed reactions.