Synthesis and Transformations of Bioactive Scaffolds via Modified Mannich and aza‐Friedel–Crafts Reactions

This account summarizes the synthesis of bifunctional glycine‐type precursors substituted with 2‐ and 1‐naphthol. The stabilization of precursors via partially aromatic ortho ‐quinone methide intermediate is tested with different cyclic imines in [4 + 2] cycloaddition. 8‐Hydroxyquinoline is a biologically active moiety considered as a formal 1‐naphthol analog, hence the behavior of the scaffold in Mannich reaction is examined. The possibility of transformation of glycine derivatives substituted with 2‐ and 1‐naphthol as well as the formed Mannich base consisting 5‐chloro‐8‐hydroxyquinoline skeleton to give diarylmethane derivatives with indole and 7‐azaindole are studied. A series of cyclic amines coupled with indole and azaindole derivatives has been systematically designed and their biological examination is achieved. To have a preliminary overview about the structure–activity relationship, the antibacterial and anticancer activity of synthesized compounds by preliminary biological screening systems is tested.