Application of Reductive Aminases in Synthesis

Abstract

Reductive amination is a key reaction used for alkylating amines, but faces limitations. These include poor atom economy resulting from a requirement for chemoselective borohydride reagents, instability of aldehyde reagents and a restricted toolbox for performing the transformation asymmetrically. In synthesis, biocatalysis has emerged as a powerful technology allowing for many important reactions to be achieved under mild conditions with excellent selectivity. The emergence of the reductive aminase sub-class of imine reductase enzymes presents an opportunity to develop an alternative to traditional reductive amination which possesses these advantages. In this thesis, the synthetic potential of these enzymes is explored through investigations into their reactivity, applications within cascade biocatalysis and the reporting of new members of the sub-class with an expanded substrate scope. As work from this PhD has been previously published in peer reviewed journals and a number of manuscripts in which the doctoral candidate was involved have either been submitted or are ready for submission, the decision was made to present this thesis in journal format. This thesis is not meant to serve as a collection of publications from this PhD, but instead contains a compilation of related manuscripts which provides a clear narrative related to the primary focus of the project.

Date of Award	31 Dec 2020
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Sabine Flitsch (Supervisor) & Nicholas Turner (Supervisor)