| Autor: |
Grabrijan K; Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia., Strašek N; Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia., Gobec S; Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia. |
| Jazyk: |
angličtina |
| Zdroj: |
International journal of molecular sciences [Int J Mol Sci] 2021 Dec 29; Vol. 23 (1). Date of Electronic Publication: 2021 Dec 29. |
| DOI: |
10.3390/ijms23010360 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
|
Nepřihlášeným uživatelům se plný text nezobrazuje |
K zobrazení výsledku je třeba se přihlásit.
|
