Development of a new methodology for the synthesis of biologically active azepine and thiepine derivatives - palladium-catalyzed double N- and S-arylation.

Razvijena je nova metoda za sintezu azepinskih i tiepinskih derivata, zasnovana na dvostrukom N- i S-arilovanju katalizovanom kompleksima paladijuma. Izborom odgovarajućeg liganda, standardizovani su reakcioni uslovi za sintezu N- i S-tricikličnih sistema u jednom koraku, polazeći iz odgovarajućih Z-stilbena. Optimizovani reakcioni uslovi primenjeni su u sintezi novih azepina i tiepina. Daljim strukturnim modifikacijama osnovnog tiepinskog sistema, sintetisani su novi tiepinski derivati. Određena je antibakterijska i antifungalna aktivnost sintetisanih jedinjenja. Ispitana je njihova toksičnost, a urađeni su i preliminarni eksperimenti s ciljem određivanja mehanizma antifungalnog dejstva tiepinskih molekula. Na osnovu dobijenih rezultata ispitivanja antifungalne aktivnosti i toksičnosti, može se zaključiti da bi testirani tiepini mogli biti osnova za razvoj novih antifungalnih terapeutika.Novel methodology for the synthesis of azepine and thiepine compounds, based on the palladium-catalyzed double N- and S-arylation reaction is reported. Reaction conditions for the preparation of N- and S-tricyclic products in one step from the appropriate stilbenes were standardized by choosing appropriate ligands. This optimized methodology was successfully applied for the synthesis of new azepine and thiepine derivatives. Structural modifications of the initial S-tricyclic core afforded a novel series of thiepine derivatives. The synthesized compounds were evaluated for their antibacterial and antifungal activities. The assessment of toxicity (lethality and teratogenicity) and preliminary tests of possible mechanism of action on the fungal cell of selected thiepines were performed. Results obtained from biological activity and toxicity screenings encourage further structure optimizations

Supplementary data for the article: Božinović, N.; Šolaja, B. A.; Opsenica, I. M. Microwave-Assisted Synthesis of Azepines via Nucleophilic Aromatic Substitution. J. Serb. Chem. Soc. 2016, 81 (11), 1225–1230. https://doi.org/10.2298/JSC160824074B

Supplementary material for: [https://doi.org/10.2298/JSC160824074B]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2354

Supplementary data for article: Božinović, N. S.; Opsenica, I.; Šolaja, B. A. Double Palladium-Catalyzed Synthesis of Azepines. Synlett 2013, 24 (1), 49–52. https://doi.org/10.1055/s-0032-1317667

Supporting information for: [https://doi.org/10.1055/s-0032-1317667]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/1597

Supplementary data for article: Šegan, S.; Božinović, N.; Opsenica, I.; Andrić, F. Consensus-Based Comparison of Chromatographic and Computationally Estimated Lipophilicity of Benzothiepino[3,2-c]Pyridine Derivatives as Potential Antifungal Drugs. Journal of Separation Science 2017, 40 (10), 2089–2096. https://doi.org/10.1002/jssc.201601442

Supporting information for: [https://doi.org/10.1002/jssc.201601442]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2462]Related to accepted version: [http://cherry.chem.bg.ac.rs/handle/123456789/3076

Supplementary data for the article: Božinović, N.; Šolaja, B. A.; Opsenica, I. M. Microwave-Assisted Synthesis of Azepines via Nucleophilic Aromatic Substitution. J. Serb. Chem. Soc. 2016, 81 (11), 1225–1230. https://doi.org/10.2298/JSC160824074B

Supplementary material for: [https://doi.org/10.2298/JSC160824074B]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2354

Microwave-assisted synthesis of azepines via nucleophilic aromatic substitution

A novel and efficient route has been developed to afford dipyridoazepine derivatives from primary amines and 3,3'-(Z)-ethene-1,2-diylbis(4-chloropyridine). The procedure based on a double nucleophilic aromatic substitution provides a valuable synthetic tool for the synthesis of dipyridoazepines. The reaction proceeds without catalyst, under microwave irradiation conditions.Supplementary material: [http://cherry.chem.bg.ac.rs/handle/123456789/3567

Supplementary data for article: Božinović, N. S.; Opsenica, I.; Šolaja, B. A. Double Palladium-Catalyzed Synthesis of Azepines. Synlett 2013, 24 (1), 49–52. https://doi.org/10.1055/s-0032-1317667

Supporting information for: [https://doi.org/10.1055/s-0032-1317667]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/1597

Supplementary data for article: Šegan, S.; Božinović, N.; Opsenica, I.; Andrić, F. Consensus-Based Comparison of Chromatographic and Computationally Estimated Lipophilicity of Benzothiepino[3,2-c]Pyridine Derivatives as Potential Antifungal Drugs. Journal of Separation Science 2017, 40 (10), 2089–2096. https://doi.org/10.1002/jssc.201601442

Supporting information for: [https://doi.org/10.1002/jssc.201601442]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2462]Related to accepted version: [http://cherry.chem.bg.ac.rs/handle/123456789/3076

Supplementary data for article: Božinović, N.; Ajdačić, V.; Lazic, J.; Lecerf, M.; Daventure, V.; Nikodinovic-Runic, J.; Opsenica, I. M.; Dimitrov, J. D. Aromatic Guanylhydrazones for the Control of Heme-Induced Antibody Polyreactivity. ACS Omega 2019, 4 (24), 20450–20458. https://doi.org/10.1021/acsomega.9b01548

Supporting information for: [https://doi.org/10.1021/acsomega.9b01548]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/3793

Supplementary data for article: Božinović, N.; Ajdačić, V.; Lazic, J.; Lecerf, M.; Daventure, V.; Nikodinovic-Runic, J.; Opsenica, I. M.; Dimitrov, J. D. Aromatic Guanylhydrazones for the Control of Heme-Induced Antibody Polyreactivity. ACS Omega 2019, 4 (24), 20450–20458. https://doi.org/10.1021/acsomega.9b01548

Supporting information for: [https://doi.org/10.1021/acsomega.9b01548]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/3793