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 . Mild acidic conditions can be used for the isomerization of -thiocarbamoyl cyanoaziridine into a 2-aminocyanothiazoline derivative by using BF·OEt as a Lewis acid. Likewise, a one pot reaction of H-cyanoaziridines with isocyanates obtained 2-iminocyanooxazolidines regioselectively. This synthetic methodology involves the addition of isocyanates to starting cyanoaziridines to obtain -carbamoyl cyanoaziridines , which after the ring opening, reacts with a second equivalent of isocyanate to give the final 2-imino cyanooxazolidines . In addition, the cytotoxic effect on the cell lines derived from human lung adenocarcinoma (A549) was also screened. 2-Iminooxazolidines exhibited moderate activity against the A549 cell line in vitro. Furthermore, a selectivity towards cancer cells (A549) over non-malignant cells (MCR-5) was detected.