Thesis
Novel biocatalytic strategies for the synthesis of N-functionalised amino acids
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2018
- Thesis identifier
- T15982
- Person Identifier (Local)
- 201456026
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- Chiral unnatural amino acids represent a class of building blocks that has gained significant attention within the pharmaceutical and agrochemical industries in recent years. Therefore, the availability of synthetic methods for novel unnatural N-protected α-amino acid derivatives is critical. Their synthesis has attracted considerable interest, however access to N-protected amino acids often requires the use of toxic reagents and hazardous solvents or stoichiometric quantities of hazardous hydrides. A number of biocatalytic approaches to chiral amino acids have been reported in recent years that provide access to this class of compounds using greener, less hazardous methodologies, however the identification of enzyme classes that could carry out reactions efficiently under industrially applicable conditions with a large substrate scope still represents a challenge. To this end, the development of a panel of novel biocatalysts to carry out reductive amination reactions for use in large scale drug synthesis has been attempted in this project. This entailed an examination of the existing wild type enzymes from three different classes (N-methylamino acid dehydrogenases, ketimine reductases and Δ1 -pyrroline5-carboxylate reductases), which required expression and screening. A variety of substrates were tested to determine the substrate scope of the enzymes. Additionally, a set of racemic product standards was selected and synthesised by chemical methods for comparison with the enzymatic products. This allowed the identification of new substrates that could be accepted for reductive amination, allowing for the synthesis of N-functionalised amino acids not previously accessible by enzyme catalysis.
- Advisor / supervisor
- Sutton, Peter (Peter W.)
- Lovelock, Sarah L.
- Watson, Allan J. B.
- Roiban, Gheorghe-Doru
- Resource Type
- Note
- Previously held under moratorium in Chemistry department (GSK) from 31st May 2018 until until 18th June 2021.
- This thesis was previously restricted to Strathclyde users only until 3rd September 2023.
- DOI
- Funder
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Contenu
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