Synthesis of 3-amino-4-substituted monocyclic ß-lactams—important structural motifs in medicinal chemistry

Grabrijan, Katarina (avtor), Strašek Benedik, Nika (avtor), Gobec, Stanislav (avtor)

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.

• Jezik: Angleški jezik
• Ključne besede: monocyclic ß-lactam, Staudinger [2+2] cyclocondensation, cerium ammonium nitrate, hydrazine hydrate, 3-amino-4-substituted azetidin-2-one, inhibitory activities
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2022
• Št. strani: 26 str.
• Številčenje: Vol. 23, iss. 1, art. 360
• PID: 20.500.12556/RUL-136778
• UDK: 615.4:54
• ISSN pri članku: 1422-0067
• DOI: 10.3390/ijms23010360
• COBISS.SI-ID: 92152323
• Datum objave v RUL: 20.05.2022

Gradivo je del revije

• Naslov: International journal of molecular sciences
• Skrajšan naslov: Int. j. mol. sci.
• Založnik: MDPI
• ISSN: 1422-0067
• COBISS.SI-ID: 2779162

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
• Začetek licenciranja: 01.01.2022

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: monociklični ß-laktam, Staudingerjeva [2+2] ciklokondenzacija, cerijev amonijev nitrat, hidrazin hidrat, 3-amino-4-substituiran azetidin-2-on, inhibitorna aktivnost, farmacevtska kemija

Projekti

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Program financ.: Young researchers

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: P1-0208
• Naslov: Farmacevtska kemija: načrtovanje, sinteza in vrednotenje učinkovin