Synthesis and Anticancer Activity of Phosphinoylated and Phosphonoylated N-Heterocycles Obtained by the Microwave-Assisted Palladium Acetate-Catalyzed Hirao Reaction.

Autor: Huszár B; Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, 1521, Budapest, Hungary., Szolga R; Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, 1521, Budapest, Hungary., Bősze S; Eötvös Loránd Research Network (ELKH), Research Group of Peptide Chemistry, Eötvös Loránd University, 1117, Budapest, Hungary., Oláhné Szabó R; Eötvös Loránd Research Network (ELKH), Research Group of Peptide Chemistry, Eötvös Loránd University, 1117, Budapest, Hungary.; Department of Genetics, Cell-and Immunobiology, Semmelweis University, 1089, Budapest, Nagyvárad tér 4, Hungary., Simon A; Department of Inorganic and Analytical Chemistry, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, 1521, Budapest, Hungary., Karaghiosoff K; Department Chemie, Ludwig-Maximilians-Universitat München, 81377, München, Butenandtstr. 5-13, Germany., Czugler M; Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, 1521, Budapest, Hungary., Drahos L; MS Proteomics Research Group, Research Centre for Natural Sciences, 1117, Budapest, Hungary., Keglevich G; Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, 1521, Budapest, Hungary.
Jazyk: angličtina
Zdroj: Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2023 Dec 06; Vol. 29 (68), pp. e202302465. Date of Electronic Publication: 2023 Oct 20.
DOI: 10.1002/chem.202302465
Abstrakt: A literature survey showed that different derivatives with the 9-phenyl-9H-carbazole or the dihydroindoline scaffold may be of biological activity including cytotoxic effect. Driven by this experience, P-functionalized derivatives of these N-heterocycles were synthesized. Three N-heterocycles, 9-(4-bromophenyl)-9H-carbazole, 3-bromo-9-phenyl-9H-carbazole and 1-(5-bromoindolin-1-yl)ethan-1-one, were coupled with dialkyl phosphites and diarylphosphine oxides using Pd(OAc) 2 (10 %) as the catalyst precursor and triethylamine as the base in ethanol under microwave irradiation. The excess of the Y 2 P(O)H reagent (Y=alkoxy, aryl) (30 %) served as the P-ligand in its trivalent tautomeric form (Y 2 POH), hence there was no need for the usual P-ligands meaning cost and environmental burden. Hence, the presented method is a "green" approach that proved to be more efficient than the preparation by the traditional method. The products, dialkyl phosphonates and tertiary phosphine oxides obtained in 58-84 % yields were characterized, one of them also by single crystal X-ray analysis, and were subjected to in vitro biological activity evaluation. A (carbazol)yl-phenylphosphonate, an N-phenyl-(carbazol)yl-phosphonate, a (carbazol)yl-phenylphosphine oxide and an N-phenyl-(carbazol)ylphosphine oxide revealed a significant cytotoxic activity on A549 human non-small-cell lung carcinoma and MonoMac-6 acute monocytic leukemia cancer cells. The cytotoxic effect was significant as compared to that of the reference compounds.
(© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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