Synthesis of heterocycles and nucleosides forming higher-order structures

Nucleic acid analogues play a multifaceted role in biology and materials science. Our efforts towards unveiling these roles led to xanthine derivatives that form higher-order structures with quadruplex-forming abilities. In this paper we present further modifications of the xanthine core resulting into 9-deaza and 8-aza-9-deaza heterocycles (pyrrolo[3,2-d]pyrimidines and pyrazolo[4,3-d]pyrimidines) that form tetrads and other higher-order structures. Additionally, the ring contraction of 2',3'-O-isopropylideneuridine gave rise to the formation of an imidazolidine-4-carboxylic acid nucleoside derivative. Our computational predictions forecasted that the latter derivative will form stable triads.