The application of diamines for amine transaminase mediated biotransformations

Gomm, Andrew (2019) The application of diamines for amine transaminase mediated biotransformations. PhD thesis, University of Nottingham.

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Abstract

Section 1 gives an overview of the importance of chiral amines, along with a short summary of important non-enzymatic catalytic methods for chiral amine synthesis. A more detailed overview of biocatalytic methods for chiral amine synthesis is provided, with a focus given to amine transaminases. Based upon this summary the aims of this PhD thesis are distilled in section 2.

Section 3 focuses on the use of aliphatic diamines as ‘smart’ diamines donors, 1,5 diaminopentane (cadaverine). The use of cadaverine allows for the effective displacement of the challenging reaction equilibria typically associated with amine transaminase mediated biotransformations. The reaction conditions were optimised and the formation of the by-product, isotripiperideine was examined. This methodology was combined with a high-throughput assay, which required the use of the diamine o-xylylenediamine, to allow for the rapid screening and subsequent scale-up of three valuable chiral amines.

Section 4 examines the use of novel o-xylylenediamine derivatives as diamines donors. The synthetic strategies for the synthesis of these compounds are outlined and their ability to act as effective amine donors are demonstrated. The use of the diamine donor 2-aminoethylaniline (2-AEA) is proposed as a potential quantitative screen for amine transaminase biotransformations. This methodology is developed to screen for both amine acceptors and amine donors and is finally developed into a solid-phase assay on agar plates.

Finally, in section 5, the use of monosaccharides as an abundant class of amine acceptors is explored. The challenges associated with analysing these biotransformations are briefly discussed. Eventually it is shown that biotransformations with these substrates can be scaled-up to high reaction concentrations (100-200 mM) and it is demonstrated that these substrates exhibit surprisingly favourable reaction equilibria.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: O'Reilly, Elaine
Keywords: Transaminase, Biocatalysis, Organic synthesis, Diamines
Subjects: Q Science > QD Chemistry > QD241 Organic chemistry > QD415 Biochemistry
Faculties/Schools: UK Campuses > Faculty of Science > School of Chemistry
Item ID: 55743
Depositing User: Gomm, Andrew
Date Deposited: 06 Jun 2019 12:55
Last Modified: 07 May 2020 13:15
URI: http://eprints.nottingham.ac.uk/id/eprint/55743

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