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.