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Manganese(III) Promoted Cyclization of N-alkenyl-N-(2-hydroxyethyl) amides to Iso-Oxacepham Potent β-Lactamase Inhibitors
Abstract
Background: β-Lactams are still a subject of interest of organic chemists. The main reason for this interest is due to their application as a chemotherapeutic. β-Lactam antibiotics are still the most commonly used drugs in bacterial infections. Method: Methods using 4-exo-trig radical cyclization leading to β-lactams are an alternative to classical Staudinger`s β-Lactams formation. We prepared N-alkenyl-N-(2-hydroxyethyl)amides to check the action of internal nucleophile. In the next step, with use of Mn(OAc)3 promoted radical cyclization 3- carbamoyl, 3-tiocarbamoyl and 3-phosphoryl β-lactams containing intramolecular nucleophile were prepared. These intermediates were able to induce the second ring closing through a carbocation trapping. Results: Iso-oxacepham derivatives were synthesized by the 4-exo-trig radical cyclization as innovative one-pot approach. Subsequent cyclization process of N-alkenyl-(2-hydroxyethyl)amides to 7- substituted iso-oxacephams was described. Influence of carbamoyl, thiocarbamoyl and phosphoryl moieties located on C-7 position of iso-oxacephamic scaffold on β-lactamase inhibitory activity was confirmed on bacterial β-lactamases from group C. Conclusion: In this paper, we describe alternative approach for the synthesis of 7-substituted isooxacepham. The hypothetic reaction mechanism for the second ring closing was confirmed. The β- lactamase inhibition was observed in case of four synthesized compounds.
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Authors (3)
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Punda Paweł Dr
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Shielmann Marta Dr
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Full text
- Publication version
- Accepted or Published Version
- DOI:
- Digital Object Identifier (open in new tab) 10.2174/1570178614666170321123252
- License
- Copyright (2017 Bentham Science Publishers)
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- Category:
- Articles
- Type:
- artykuł w czasopiśmie wyróżnionym w JCR
- Published in:
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LETTERS IN ORGANIC CHEMISTRY
no. 14,
edition 5,
pages 337 - 346,
ISSN: 1570-1786 - Language:
- English
- Publication year:
- 2017
- Bibliographic description:
- Paweł P., Marta S., Makowiec S.: Manganese(III) Promoted Cyclization of N-alkenyl-N-(2-hydroxyethyl) amides to Iso-Oxacepham Potent β-Lactamase Inhibitors// LETTERS IN ORGANIC CHEMISTRY. -Vol. 14, iss. 5 (2017), s.337-346
- DOI:
- Digital Object Identifier (open in new tab) 10.2174/1570178614666170321123252
- Verified by:
- Gdańsk University of Technology
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