DIVERGENT, PHOTOCHEMICAL EDITING OF CHIRAL FUSED-URACIL DERIVATIVES IN SEARCH OF NOVEL ANTIVIRAL SCAFFOLDS

The growing need for new antiviral agents, driven by recurrent pandemics and epidemics, has prompted the development of structurally innovative small molecules with improved biological profiles. Chiral 7,8-dihydroquinazolin- 2,4-diones 1, readily accessible through our previously reported enantioselective organocatalytic strategy, represent promising antiviral scaffolds. To further expand their chemical and biological potential, we explored late-stage photochemical modifications of the carbofused ring system. This work investigated two complementary photochemical approaches on the dihydroquinazolinone scaffold: i) photoaromatization of the carbofused system and ii) site-selective C8-functionalization to improve scaffold stability and diversify the molecular framework while preserving stereochemical integrity. Photoaromatization was achieved under blue LED irradiation in the presence of a suitable amine. The site-selective alkylation strategy involved a one-pot/two-step sequence based on the in situ generation of a silyl trienol ether orthoquinodimethane (oQDM) intermediate 3, followed by photoredox-mediated radical alkylation under blue LED irradiation using suitable radical precursors and a photocatalyst. Both transformations were optimized in terms of efficiency and reaction conditions.