Wu, Jingyue;
(2025)
Stereoselective synthesis of
chiral sulfur compounds via
biocatalytic strategies.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Chiral sulfur compounds present and play an important role in a wide range of chemistry sectors, with their chirality being crucial to their efficacy and versatility. However, achieving precise control over the chirality of these compounds remains a challenge due to the unique reactivity of sulfur. Current approaches employing metal- or organocatalysts often face limitations, including pricy, toxicity, and the risk of contamination in final products, which conflict with the principles of green chemistry. With the rapid development of molecular biology in recent decades, the biocatalyst toolbox has expanded significantly, offering new opportunities for greener and more sustainable catalysis. In this thesis, two classes of biocatalysts—monooxygenases and lactonases—were employed to develop innovative methodologies for the enantioselective synthesis of sulfur-containing compounds. Firstly, the substrate scope of Baeyer-Villiger monooxygenases (BVMOs) and flavin-containing monooxygenases (FMOs) was successfully expanded, enabling the enantiodivergent synthesis of optically pure sulfoxides with excellent enantioselectivity (ee up to 99%). Secondly, lactonases, a less explored enzyme class in biocatalysis, were investigated to resolve homocysteine thiolactones and an enzymatic kinetic resolution with excellent enantioselectivity was established with lactonase GcL. Finally, rationally designed lactonases from a reconstructed ancestor enzyme of PON lactonases were used for the dynamic kinetic resolution of 3-thio substituted thiolactones, yielding the corresponding thiocarboxylic acids with excellent conversion of up to >99% and ee of up to >99%. Additionally, computational analyses and site-directed mutagenesis provided mechanistic insights into the roles of residues in the biotransformations. These findings indicated the potential of biocatalysis for the sustainable production of chiral sulfur compounds, aligning with the goals of green chemistry.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Stereoselective synthesis of chiral sulfur compounds via biocatalytic strategies |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2025. 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 UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10207954 |
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