Organocatalytic atroposelective de novo construction of monoaxially and 1,4-diaxially chiral fused uracils with potential antitumor activity†

Abstract

Atropisomers bearing multiple stereogenic axes are of increasing relevance to materials science, pharmaceuticals, and catalysis. However, the catalytic enantioselective construction of these atropisomers in a single step remains synthetically challenging. We herein report the first NHC-organocatalytic enantioselective synthesis of a new class of monoaxially and 1,4-diaxially chiral fused uracil scaffolds. Preliminary studies on the antitumor activity of selected compounds demonstrated that this new class of axially chiral uracil derivatives may have potential applications in the discovery of new lead compounds in medicinal chemistry.