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) (10 %) as the catalyst precursor and triethylamine as the base in ethanol under microwave irradiation. The excess of the Y P(O)H reagent (Y=alkoxy, aryl) (30 %) served as the P-ligand in its trivalent tautomeric form (Y 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.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1002/chem.202302465 | DOI Listing |
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!