Anselmi, Silvia;
(2023)
Development of unconventional biocatalytic strategies for the synthesis of sulfoxides.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
The synthesis of sulfoxides represents an ongoing challenge for the scientific community as these molecules find many applications in chemistry, varying from organic synthesis to medicinal chemistry. With the aim of providing a solution to the toxic and hazardous methods classically used for the synthesis of sulfoxides, biocatalysis has emerged in the past several decades as an alternative green and sustainable strategy to obtain both racemic and enantiopure sulfoxides. However, the use of enzymes still has some drawbacks, especially in terms of industrial applicability, as they often work on laboratory scale only, may lead to the production of other oxidative side products, or require the use of expensive cofactors and effective oxygenation. In this thesis, three different biocatalytic approaches for the synthesis of sulfoxides applicable in both academic and industrial settings are illustrated. First, the immobilised enzyme Candida antarctica lipase B was exploited to develop a mild, chemoselective and sustainable biocatalytic method, suitable for industrial use, for the preparation of sulfoxides from sulfides. Second, Baeyer-Villiger and flavine monooxygenases were investigated for the production of enantiopure sulfoxides that display multiple functional groups. Lastly, the reductive enzyme methionine sulfoxide reductase A (MsrA) from Saccharomyces cerevisiae was employed for the kinetic resolution of racemic sulfoxides using the inexpensive recycling co-substrate dithiothreitol and a total of 23 (R)-sulfoxides were obtained with excellent enantiomeric excess and yields. Additionally, the catalytic mechanism of the enzyme was investigated in depth via structural biology, mutagenesis, and in silico studies, which also led to the development of a new engineered MsrA biocatalyst capable of reducing bulky substrates.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Development of unconventional biocatalytic strategies for the synthesis of sulfoxides |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2023. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10173571 |
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