Development of biocatalytic approaches and screening methodology for the synthesis of nitrogen-containing small molecules

Cairns, Ryan (2022) Development of biocatalytic approaches and screening methodology for the synthesis of nitrogen-containing small molecules. PhD thesis, University of Nottingham.

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Abstract

As we move towards a more sustainable global economy, there is a need to develop efficient methods for the synthesis of key chiral molecules that are particularly vital for the pharmaceutical and agrochemical industries. Catalysis has opened up a plethora of synthetic opportunities and biocatalytsis, specifically, has now emerged as a sustainable alternative to other catalytic approaches. The application of amine transaminases (ATAs) for the conversion of pro-chiral carbonyls to the corresponding chiral amines in the presence of a suitable amine donor and the coenzyme pyridoxyl-5’-phosphate (PLP) has been well established. While their commonly cited limitations include narrow substrate scope and/or incompatible operational temperatures/pH, there is significant literature precedent for overcoming these challenges through enzyme engineering endeavours, which typically require reliable, high throughput selection assays.

The O’Reilly group is interested in the biocatalytic synthesis of iminosugars from simple monosaccharides. The approach relies on the biocatalytic conversion of a monosaccharide, such as D-deoxygalactose (A1), to the corresponding aminopolyol A2 (Scheme A1) using an ATA. Following installation of the amine, regioselective biocatalytic oxidation and spontaneous cyclisation would afford cyclic imine A3, which could be selectively reduced to the desired iminosugar A4. The work presented in this thesis will predominantly focus on the first step of this process, the enzymatic transamination.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: O'Reilly, Elaine
Keywords: Nitrogen-containing small molecules, Synthesis, Biocatalytsis
Subjects: Q Science > QP Physiology > QP501 Animal biochemistry
Faculties/Schools: UK Campuses > Faculty of Science > School of Chemistry
Item ID: 68383
Depositing User: Cairns, Ryan
Date Deposited: 02 Aug 2022 04:40
Last Modified: 02 Aug 2022 04:40
URI: http://eprints.nottingham.ac.uk/id/eprint/68383

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