20.500.12556/RUL-136778 Synthesis of 3-amino-4-substituted monocyclic ß-lactams—important structural motifs in medicinal chemistry Monocyclic ß-lactams (azetidin-2-ones) exhibit a wide range of biological activities, the most important of which are antibacterial, anticancer, and cholesterol absorption inhibitory activities. The synthesis of decorated monocyclic ß-lactams is challenging because their ring is highly constrained and consequently reactive, which is also an important determinant of their biological activity. We present the optimized synthesis of orthogonally protected 3-amino-4-substituted monocyclic ß-lactams. Among several possible synthetic approaches, Staudinger cycloaddition proved to be the most promising method for initial ring formation, yielding monocyclic ß-lactams with different substituents at the C-4 position, a phthalimido-protected 3-amino group, and a (dimethoxy)benzyl protected ring nitrogen. Challenging deprotection methods were then investigated. Oxidative cleavage with cerium ammonium nitrate and ammonia-free Birch reduction was found to be most effective for selective removal of ring nitrogen protection. Hydrazine hydrate was used for deprotection of the phthalimido group, and the procedure had to be modified by the addition of HCl in the case of aromatic substituents at the C-4 position. The presented methods and the synthesized 3-amino-4-substituted monocyclic ß-lactam derivatives are an important step toward new ß-lactams with potential pharmacological activities. monocyclic ß-lactam Staudinger [2+2] cyclocondensation cerium ammonium nitrate hydrazine hydrate 3-amino-4-substituted azetidin-2-one inhibitory activities monociklični ß-laktam Staudingerjeva [2+2] ciklokondenzacija cerijev amonijev nitrat hidrazin hidrat 3-amino-4-substituiran azetidin-2-on inhibitorna aktivnost farmacevtska kemija true false true Angleški jezik Slovenski jezik Članek v reviji 2022-05-20 11:48:28 2022-05-20 11:48:33 2022-09-15 04:14:19 0000-00-00 00:00:00 2022 0 0 26 str. iss. 1, art. 360 Vol. 23 2022 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 615.4:54 1422-0067 10.3390/ijms23010360 92152323 ijms-23-00360-v2.pdf ijms-23-00360-v2.pdf 1 B8E754148E25936B066BFC1AC7DD6BE7 3493b41342c93c346f04eaffb76db61bf03668a255bce5f8cd68fbc02a3d9e8f 2af4f6df-d825-11ec-8aca-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=156564 https://www.mdpi.com/1422-0067/23/1/360 1 e43f6772-d821-11ec-8aca-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=156561 Fakulteta za farmacijo 0 0 0