Department of Organic Chemistry I, Faculty of Pharmacy and Lascaray Research Center, University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, 01006 Vitoria, Spain.
Molecules. 2021 Jul 14;26(14):4265. doi: 10.3390/molecules26144265.
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.
几种磷取代的酰基氰氮丙啶和氨甲酰基氰氮丙啶以高产率制备。经扩环后，酰基氰氮丙啶用于高效合成恶唑啉衍生物，并在碘化钠存在下进行完全区域控制反应。相反，氨甲酰基氰氮丙啶与碘化钠反应，得到 2-氨基氰基恶唑啉的区域异构体混合物。在使用 BF·OEt 作为路易斯酸的情况下，温和的酸性条件可用于将 -硫代氨甲酰基氰氮丙啶异构化为 2-氨基氰基噻唑啉衍生物。同样，氰基氮丙啶与异氰酸酯的一锅反应以区域选择性得到 2-亚氨基氰基恶唑啉。这种合成方法涉及异氰酸酯与起始氰氮丙啶的加成，得到氨甲酰基氰氮丙啶，然后在开环后，与第二当量的异氰酸酯反应，得到最终的 2-亚氨基氰基恶唑啉。此外，还对人肺腺癌（A549）来源的细胞系进行了细胞毒性筛选。2-亚氨基恶唑啉在体外对 A549 细胞系表现出中等活性。此外，还检测到对癌细胞（A549）的选择性，而对非恶性细胞（MCR-5）没有选择性。
