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

Nicola Piens (UGent)
(2017)
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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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MLA
Piens, Nicola. “Synthesis of New Β-lactam Building Blocks and Their Application in Heterocyclic Chemistry.” 2017 : n. pag. Print.
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},
}