- Author
- Nicola Piens
- Promoter
- Matthias D'hooghe (UGent)
- Organization
- Abstract
- Within azaheterocyclic chemistry, β-lactams comprise an extraordinary class of strained compounds with diverse applications. In addition to their biological importance as potent antibiotics, azetidin-2-ones have been recognized as valuable building blocks for further elaboration toward a variety of nitrogen-containing structures. In a major part of this PhD thesis, the cobalt carbonyl-catalyzed carbonylation of different classes of non-activated aziridines was scrutinized, with special attention devoted to selectivity issues and reaction optimization. This has resulted in the regio- and stereoselective synthesis of 24 novel β-lactam target structures in high yields on a multigram scale, which were subjected to selected ring-expansion, ring-closure and side chain-functionalization protocols. In addition, other emerging topics have been covered in this thesis, including the synthesis of β-lactam-based hybrids and C-fused bicyclic β-lactams. In particular, trimethylene-tethered thymine-(bis-)β-lactam chimeras were prepared and subsequently assessed for their antiviral activity, cytotoxicity and cytostatic activity. Furthermore, 4-(3-aryloxiran-2-yl)azetidin-2-ones were synthesized in a highly diastereoselective way and converted into a novel class of 3,4-oxolane-fused bicyclic β-lactams, providing interesting leads for further β-lactamase inhibitor development. Finally, the reactivity of 3-oxo-β-lactams with respect to primary amines was explored in-depth, both experimentally and computationally. Depending on the different β-lactam substituents, this reaction was shown to selectively produce 3-imino-β-lactams (dehydration products), α-aminoamides (CO elimination products) or unprecedented ethanediamides (C3-C4 ring-opening products).
- Keywords
- β-Lactams, Nitrogen heterocycles, Reactivity, Bioactivity, Homogeneous catalysis
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-8525607
- MLA
- Piens, Nicola. Synthesis of New β-Lactam Building Blocks and Their Application in Heterocyclic Chemistry. Ghent University. Faculty of Bioscience Engineering, 2017.
- APA
- Piens, N. (2017). Synthesis of new β-lactam building blocks and their application in heterocyclic chemistry. Ghent University. Faculty of Bioscience Engineering, Ghent, Belgium.
- Chicago author-date
- Piens, Nicola. 2017. “Synthesis of New β-Lactam Building Blocks and Their Application in Heterocyclic Chemistry.” Ghent, Belgium: Ghent University. Faculty of Bioscience Engineering.
- Chicago author-date (all authors)
- Piens, Nicola. 2017. “Synthesis of New β-Lactam Building Blocks and Their Application in Heterocyclic Chemistry.” Ghent, Belgium: Ghent University. Faculty of Bioscience Engineering.
- Vancouver
- 1.Piens N. Synthesis of new β-lactam building blocks and their application in heterocyclic chemistry. [Ghent, Belgium]: Ghent University. Faculty of Bioscience Engineering; 2017.
- IEEE
- [1]N. Piens, “Synthesis of new β-lactam building blocks and their application in heterocyclic chemistry,” Ghent University. Faculty of Bioscience Engineering, Ghent, Belgium, 2017.
@phdthesis{8525607, abstract = {{Within azaheterocyclic chemistry, β-lactams comprise an extraordinary class of strained compounds with diverse applications. In addition to their biological importance as potent antibiotics, azetidin-2-ones have been recognized as valuable building blocks for further elaboration toward a variety of nitrogen-containing structures. In a major part of this PhD thesis, the cobalt carbonyl-catalyzed carbonylation of different classes of non-activated aziridines was scrutinized, with special attention devoted to selectivity issues and reaction optimization. This has resulted in the regio- and stereoselective synthesis of 24 novel β-lactam target structures in high yields on a multigram scale, which were subjected to selected ring-expansion, ring-closure and side chain-functionalization protocols. In addition, other emerging topics have been covered in this thesis, including the synthesis of β-lactam-based hybrids and C-fused bicyclic β-lactams. In particular, trimethylene-tethered thymine-(bis-)β-lactam chimeras were prepared and subsequently assessed for their antiviral activity, cytotoxicity and cytostatic activity. Furthermore, 4-(3-aryloxiran-2-yl)azetidin-2-ones were synthesized in a highly diastereoselective way and converted into a novel class of 3,4-oxolane-fused bicyclic β-lactams, providing interesting leads for further β-lactamase inhibitor development. Finally, the reactivity of 3-oxo-β-lactams with respect to primary amines was explored in-depth, both experimentally and computationally. Depending on the different β-lactam substituents, this reaction was shown to selectively produce 3-imino-β-lactams (dehydration products), α-aminoamides (CO elimination products) or unprecedented ethanediamides (C3-C4 ring-opening products).}}, author = {{Piens, Nicola}}, isbn = {{9789463570077}}, keywords = {{β-Lactams,Nitrogen heterocycles,Reactivity,Bioactivity,Homogeneous catalysis}}, language = {{eng}}, pages = {{VI, 185}}, publisher = {{Ghent University. Faculty of Bioscience Engineering}}, school = {{Ghent University}}, title = {{Synthesis of new β-lactam building blocks and their application in heterocyclic chemistry}}, year = {{2017}}, }