ИСТИНА

Isatin (indoline-2,3-dione) derivatives are widely used for the synthesis of various heterocyclic compounds which demonstrate different kinds of biological activity: antibacterial, antiprotozoal, antifungal, antiviral, anti-HIV, anticonvulsant and antihelminthic activities, influence CNS, participate in metabolism and stimulate the growth of plants. In our research group, we have developed an efficient and practical technique for the synthesis of 5-arylsubstituted isatins employing palladium catalyzed Suzuki cross-coupling reaction as a key step. Our synthesis commenced with the preparation of 5-bromoisatin 2 from commercially available isatin 1 by heating it with Br2 in acetic acid. Then, 5-bromoisatin 2 was treated with inorganic base (K2CO3 or NaOH) in an ethanol–water mixture. After hydrolysis of initially formed N-anion (dark red color) an oxoacid anion 3 was obtained (transparent solution). At this point, arylboronic acids and palladium catalyst (Pd(dppf)Cl2, 1÷5 mol.-%) were added to the reaction flask. Acidification of anions 4 with acetic acid furnished target compounds. As a result, a small library of 5-aryl-isatins 5 (30 examples) was synthesized.In collaboration with scientists from Italy the 5-aryl-isatine scaffold was identified to be a practical research tool for the design and realization of novel, potent and selective matrix metalloproteinases (MMPs) inhibiting agents, which could provide novel approaches to anticancer treatments.