A Palladium-Catalyzed Carbonylation Approach to Eight-Membered Lactam Derivatives with Antitumor Activity.
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| Abstract |
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.
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| Authors | Raffaella Mancuso, Dnyaneshwar S Raut, Nadia Marino, Giorgio De Luca, Cinzia Giordano, Stefania Catalano, Ines Barone, Sebastiano Andò, Bartolo Gabriele |
| Journal | Chemistry (Weinheim an der Bergstrasse, Germany) (Chemistry) Vol. 22 Issue 9 Pg. 3053-64 (Feb 24 2016) ISSN: 1521-3765 [Electronic] Germany |
| PMID | 26821986 (Publication Type: Journal Article) |
| Copyright | © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
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