SUSTAINABLE CHEMISTRY FOR THE PREPARATION OF NITROGENATED POLYHETEROCYCLIC SYSTEMS OF BIOLOGICAL INTEREST

The palladium and platinum catalyzed intramolecular reactions of unsaturated systems (alkynes, alkenes and allenes) arising from commercially available o-aminophenols and o-nitroaniline have been studied. Both carbo- and hydroamination processes resulted in the formation of nitrogen- benzofused rings. The carboamination domino process led to the C–C and C–N bond formation using a wide variety of aryl- and heteroaryl halides. The regioselectivity of the cyclization step was strongly dependent on the unsaturated system and on the protecting group tethered to the nitrogen atoms, allowing the formation of five- six- and seven-membered rings. In the second part, applications of two specific processes the Buchwald-Hartwig and Ullmann-type reactions were reported. The first process allowed the synthesis of a particular class of heteropolycyclic systems endowed with pharmacological properties as anticancer. The synthesis of the new hexacyclic system was realized starting from tryptamines and exploiting as a key step a sequential Pd-catalyzed N-arylation/acylation reaction. Having topoisomerases as biological target and the campthotecins class as benchmark, the new scaffold was decorated with substituents having different polarity and tested as Topoisomerase I inhibitors. The copper catalyzed Ullmann-type reaction was exploited to afford oxazino-indole scaffold through the intramolecular C-O bond formation, starting from N-hydroxyethyl-isatin derivatives.