engleski

Novel Conjugates of 1, 2, 3-Triazoles and Acyclic Pyrimidine Nucleoside Analogues via Click Reaction

Nucleosides bearing a five-membered heterocyclic bases have become interesting objects to design and synthesize since the discovery of antiviral potency of 1, 2, 4-triazole ring derivative ribavirin. The structural variations of ribavirin have led to analogues bound with 1, 2, 3-triazole ring, which can be extremely easily prepared. The synthesis of novel acyclic pyrimidine nucleoside analogues with 1, 2, 3-triazole ring bound via ethylene spacer or directly to C-5 of pyrimidine ring will be presented. 1, 4-Disubstituted 1, 2, 3-triazoles were synthesized by click chemistry approach using regioselective copper(I)-catalyzed 1, 3-dipolar cycloaddition reaction between terminal alkyne and azido pyrimidines under both conventional (method A) and microwave (method B) conditions. N-Alkylation of triazolyl pyrimidines afforded 5-[2-(1, 2, 3-triazolyl)ethyl]pyrimidine derivatives with penciclovir-, ganciclovir-like and 2, 3-dihydroxypropyl side chain, as well as 5-(1, 2, 3-triazolyl)pyrimidine derivatives with penciclovir- and ganciclovir-like side chain. The stereostructures of 2-hydroxyethyl, 2-tosyloxyethyl, 2-azidoethyl and 4-acetoxymethyl-1, 2, 3-triazolyl C-5 substituted pyrimidine derivatives were unambiguously confirmed by their X-ray crystal structure analysis. The cytostatic evaluations in vitro against breast carcinoma (MCF-7), colon carcinoma (HCT116) and lung carcinoma (H 460) of synthesized conjugates will be also presented.

Acyclic pyrimidine nucleoside; azide-alkyne cycloaddition; click chemistry; 1; 4-disubstituted 1; 2; 3-triazoles; X-ray diffraction

nije evidentirano