Synthesis of α-Aminophosphonic Acid Derivatives Through the Addition of O - and S -Nucleophiles to 2 H -Azirines and Their Antiproliferative Effect on A549 Human Lung Adenocarcinoma Cells.

Autor: Carramiñana V; Department of Organic Chemistry I, Faculty of Pharmacy and Lascaray Research Center, University of the Basque Country (UPV/EHU), 01006 Vitoria, Spain., Ochoa de Retana AM; Department of Organic Chemistry I, Faculty of Pharmacy and Lascaray Research Center, University of the Basque Country (UPV/EHU), 01006 Vitoria, Spain., Palacios F; Department of Organic Chemistry I, Faculty of Pharmacy and Lascaray Research Center, University of the Basque Country (UPV/EHU), 01006 Vitoria, Spain., de Los Santos JM; Department of Organic Chemistry I, Faculty of Pharmacy and Lascaray Research Center, University of the Basque Country (UPV/EHU), 01006 Vitoria, Spain.
Jazyk: angličtina
Zdroj: Molecules (Basel, Switzerland) [Molecules] 2020 Jul 22; Vol. 25 (15). Date of Electronic Publication: 2020 Jul 22.
DOI: 10.3390/molecules25153332
Abstrakt: This work reports a straightforward regioselective synthetic methodology to prepare α-aminophosphine oxides and phosphonates through the addition of oxygen and sulfur nucleophiles to the C-N double bond of 2 H -azirine derivatives. Determined by the nature of the nucleophile, different α-aminophosphorus compounds may be obtained. For instance, aliphatic alcohols such as methanol or ethanol afford α-aminophosphine oxide and phosphonate acetals after N-C3 ring opening of the intermediate aziridine. However, addition of 2,2,2-trifluoroethanol, phenols, substituted benzenthiols or ethanethiol to 2 H -azirine phosphine oxides or phosphonates yields allylic α-aminophosphine oxides and phosphonates in good to high general yields. In some cases, the intermediate aziridine attained by the nucleophilic addition of O - or S -nucleophiles to the starting 2 H -azirine may be isolated and characterized before ring opening. Additionally, the cytotoxic effect on cell lines derived from human lung adenocarcinoma (A549) and non-malignant cells (MCR-5) was also screened. Some α-aminophosphorus derivatives exhibited very good activity against the A549 cell line in vitro. Furthermore, selectivity towards cancer cell (A549) over non-malignant cells (MCR-5) has been detected in almost all compounds tested.
Databáze: MEDLINE
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