engleski

Synthesis of Novel C-8 Substituted Purine Derivatives - Potential Antiviral Agents

Acyclic analogs of guanosine are a unique class of heterocyclic compounds, and are of interest as potentially biologically active substances and also as models for investigation of molecular interactions in synthetic systems. Since the effect of C8 substitution on the antiviral activity was studied in the case of acyclovir analogues, we were interested in developing the synthesis of several 8-(4-substituted-1H-1, 2, 3-triazol-1-yl)guanine derivatives. Our approach to modified nucleoside derivatives involves the functionalisation of guanosine and acyclovir in the C-8 position with differently 4-substituted triazole rings by using a 1, 4-regioselective copper-catalyzed azide/alkyne cycloaddition (CuAAC). In the first step the starting materials were converted into the 8-halogen derivatives and than in a two steps required azides were prepared. Next step was so-called “click” reaction, which resulted in formation of the regiospecific 1, 4-isomers using various terminal alkynes. Taken together, our results illustrate the efficiency of the given synthetic methodology for the supply of a variety of 8-(4-substituted-1H-1, 2, 3-triazol-1-yl)guanine derivatives for further biophysical and biological applications. The evaluation of the antiviral activity of these analogues is under investigation.

C8 Substituted Purine Derivatives; Triazoles; Antiviral Agents

nije evidentirano