A Palladium-Catalyzed Carbonylation Approach to Eight-Membered Lactam Derivatives with Antitumor Activity.

Autor: Mancuso R; Laboratory of Industrial and Synthetic Organic Chemistry (LISOC), Department of Chemistry and Chemical Technologies, University of Calabria, Via Pietro Bucci, 12/C, 87036, Arcavacata di Rende (CS), Italy. raffaella.mancuso@unical.it., Raut DS; Laboratory of Industrial and Synthetic Organic Chemistry (LISOC), Department of Chemistry and Chemical Technologies, University of Calabria, Via Pietro Bucci, 12/C, 87036, Arcavacata di Rende (CS), Italy., Marino N; Department of Chemistry and Chemical Technologies, University of Calabria, Via Pietro Bucci, 14/C, 87036, Arcavacata di Rende (CS), Italy., De Luca G; Institute on Membrane Technology, National Research Council, Via Pietro Bucci, 17/C, 87036, Arcavacata di Rende (CS), Italy., Giordano C; Health Center and Department of Pharmacy, and Health and Nutritional Science, University of Calabria, 87036, Arcavacata di Rende (CS), Italy., Catalano S; Health Center and Department of Pharmacy, and Health and Nutritional Science, University of Calabria, 87036, Arcavacata di Rende (CS), Italy., Barone I; Health Center and Department of Pharmacy, and Health and Nutritional Science, University of Calabria, 87036, Arcavacata di Rende (CS), Italy., Andò S; Health Center and Department of Pharmacy, and Health and Nutritional Science, University of Calabria, 87036, Arcavacata di Rende (CS), Italy., Gabriele B; Laboratory of Industrial and Synthetic Organic Chemistry (LISOC), Department of Chemistry and Chemical Technologies, University of Calabria, Via Pietro Bucci, 12/C, 87036, Arcavacata di Rende (CS), Italy. bartolo.gabriele@unical.it.
Jazyk: angličtina
Zdroj: Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2016 Feb 24; Vol. 22 (9), pp. 3053-64. Date of Electronic Publication: 2016 Jan 28.
DOI: 10.1002/chem.201504443
Abstrakt: The reactivity of 2-(2-alkynylphenoxy)anilines under PdI2 /KI-catalyzed oxidative carbonylation conditions has been studied. Although a different reaction pathway could have been operating, N-palladation followed by CO insertion was the favored pathway with all substrates tested, including those containing an internal or terminal triple bond. This led to the formation of a carbamoylpalladium species, the fate of which, as predicted by theoretical calculations, strongly depended on the nature of the substituent on the triple bond. In particular, 8-endo-dig cyclization preferentially occurred when the triple bond was terminal, leading to the formation of carbonylated ζ-lactam derivatives, the structures of which have been confirmed by XRD analysis. These novel medium-sized heterocyclic compounds showed antitumor activity against both estrogen receptor-positive (MCF-7) and triple negative (MDA-MB-231) breast cancer cell lines. In particular, ζ-lactam 3 j' may represent a novel and promising antitumor agent because biological tests clearly demonstrate that this compound significantly reduces cell viability and motility in both MCF-7 and MDA-MB-231 breast cancer cell lines, without affecting normal breast epithelial cell viability.
(© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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