Bicyclic nucleoside analogues: synthesis of thiazolopyrimidine-based nucleosides via a copper-catalysed tandem reaction of 5-iodocytidine with isothiocyanates†

Abstract

We have devised a copper-catalysed tandem annulation reaction to generate a new class of bicyclic nucleoside analogues (BCNAs), namely, amino-substituted thiazolopyrimidine ribonucleosides. The reaction between triacetyl-5-iodo-cytidine and an appropriate organic isothiocyanate in the presence of a Cu salt and ligand resulted in the formation of an amino-substituted thiazolopyrimidine moiety. This reaction was found to be compatible with a range of aliphatic and aromatic isothiocyanates, affording the corresponding products in moderate to good yields. The methodology was extended to diacetyl-2′-deoxy-5-iodo-cytidine and we could also establish the applicability of the methodology on a gram scale. Finally, acetyl deprotection of amino-substituted thiazolopyrimidine ribonucleosides was achieved by treatment with NH₃ in MeOH.