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Synthesis of new β-lactam building blocks and their application in heterocyclic chemistry

(2017)
Author
Promoter
(UGent)
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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:

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}},
}