Synthesis and Antiproliferative Activity of Phosphorus Substituted 4-Cyanooxazolines, 2-Aminocyanooxazolines, 2-Iminocyanooxazolidines and 2-Aminocyanothiazolines by Rearrangement of Cyanoaziridines.

Several phosphorus-substituted -acylated cyanoaziridines and -carbamoylated cyanoziridines were prepared in good to high yields. -Acylated cyanoaziridines were used, after ring expansion, in an efficient synthesis of oxazoline derivative and in a completely regio-controlled reaction in the presence of NaI. Conversely, -carbamoyl cyanoaziridines reacted with NaI to obtain a regioisomeric mixture of 2-aminocyanooxazolines .

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

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-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.

First synthesis of merged hybrids phosphorylated azirino[2,1-b]benzo[e][1,3]oxazine derivatives as anticancer agents.

This work describes a straightforward diastereoselective synthetic access to azirino[2,1-b]benzo[e][1,3]oxazines containing phosphorus substituents such as phosphonate or phosphine oxide, by means of nucleophilic addition of functionalized phenols to the C-N double bond of 2H-azirine derivatives. In addition, the cytotoxic effect on cell lines derived from human lung adenocarcinoma (A549) and human embryonic kidney (HEK293) was also screened. Some azirino[2,1-b]benzo[e][1,3]oxazines 4 and 6 exhibited very good activity against the A549 cell line in vitro.

Synthesis and biological evaluation of cyanoaziridine phosphine oxides and phosphonates with antiproliferative activity.

This work reports an efficient diastereoselective synthetic methodology for the preparation of phosphorus substituted cyanoaziridines through the nucleophilic addition of TMSCN, as cyanide source, to the C-N double bond of 2H-azirine derivatives. The aziridine ring, in these novel cyanoaziridines, can be activated by simple N-tosylation or N-acylation. In addition, the cytotoxic effect on cell lines derived from human lung adenocarcinoma (A549) and human embryonic kidney (HEK293) was also screened.