Synthetic and biological applications of tricyclic analogues of guanosine.

Abstract

Tricyclic nucleosides incorporating the 9-oxo-imidazo [1,2-a]purine (1,N2-ethenoguanine) system, natural prototypes of which occur in tRNA(Phe) as nucleosides of the wyosine series, were used for synthetic, structural and biological purposes. 1,N2-(Prop-1-ene-1,2-diyl)guanosine derivatives used as intermediates allowed to enforce on guanosine the substitution at the N-3 position and at the N2 exo-amino group, not possible to be performed directly. Wyosine and 2'-deoxywyosine together with 4,5'-anhydro-4-desmethylwyosine and its congeners were used as, respectively, 100% anti and 100% syn conformation standards in a new graphical method for the syn-anti conformational analysis of nucleosides by 1D 1H NOE difference spectroscopy. Substitution at the appended third ring allowed to modify the biological and physical properties of antiviral agents acyclovir and ganciclovir, e.g. to develop their fluorescent analogues.