Palladium-catalyzed coupling reactions of uracil nucleosides and nucleotides

Abstract

A new method is described for the facile alkylation of uracil nucleotides. Treatment of the unprotected nucleotide with mercuric acetate followed by the addition of styrene or ring-substituted styrenes and lithium tetrachloropalladate affords the C-5-trans-styryl derivatives. The coupling reactions using nucleosides or nucleotides proceed in moderate to good yield, can be run in protic solvents, are not adversely affected by the presence of the phosphate group or sugar hydroxyls, and are compatible with nitro, amino, and azido substitution of the phenyl ring in styrene.

Substrate and Mispairing Properties of 5-Formyl-2'-Deoxyuridine 5'-Triphosphate Assessed by in vitro DNA Polymerase Reactions

“…In this context, whether resulting from oxidation of thymine in dTTP or DNA, fU is expected to be potentially mutagenic. The potential genotoxicity associated with fU may also explain why repair enzymes removing this lesion from damaged DNA exist in cells (24,25,38).…”

“…fdUMP was prepared following the reported method (37) with a slight modification. 2′-Deoxyuridine 5′-monophosphate (dUMP) was converted to 5-acetoxymercuri-2′-deoxyuridine 5′-monophosphate, then to 5(E)-styryl-2′-deoxyuridine 5′-monophosphate (SdUMP) (37,38). Oxidative cleavage of the 5-vinylic bond of SdUMP yielded fdUMP.…”

Synthetic Nucleosides and Nucleotides. 37. Antisense Oligodeoxynucleotides Bearing 5-(Phenylethyl)-2′-deoxyuridylate at the 3′-Terminus: Exonuclease-Resistant Molecule with Natural Phosphodiester Backbone

“…Chemistrys2′-Deoxy-5-(2-phenylethyl)uridine (1) was synthesized following the method reported by Bergstrom et al 22 and Bigge et al 23 Dimethoxytritylated (DMT) 1 (2) was phosphitylated to give the cyanoethyl phosphoramidite (3) in 89% yield as a diastereoisomeric mixture. To introduce the modified nucleotide at the 3′-terminal of ODNs, the 3′-hydroxy group of 1 was esterified with 4-[2-(benzyloxy)-ethyl]benzoic acid and converted to the corresponding cyanoethyl phosphoramidite (8) as shown in Scheme 1.…”

Palladium-Catalyzed Modification of Unprotected Nucleosides, Nucleotides, and Oligonucleotides

“…The earliest examples of cross-coupling of unprotected nucleosides were promoted by ligand-free palladium salts in polar organic solvents. Mertes reported a Heck-type coupling of 5-(HgCl)dU with styrene derivatives mediated by stoichiometric Li 2 PdCl 4 in methanol to give 5-alkenyl-dU compounds (Scheme 2) [23]. The method was also applied to 5-(HgOAc)dUMP.…”