Biocatalytic Imine Reduction and Reductive Amination

UoM administered thesis: Phd

  • Authors:
  • Scott France

Abstract

Chiral amine motifs are found in many bioactive compounds and therefore strategies for their direct asymmetric synthesis are of great interest. Alongside traditional chemical methods, biocatalysis serves as an important tool for the formation of these compounds that can confer the benefits of sustainable catalyst supply and mild reaction conditions. This thesis describes the application of imine reductase (IRED) biocatalysts for the asymmetric reduction of pre-formed imines and the reductive amination of carbonyl compounds to produce chiral amines. These enzymes are relatively recent additions to the toolbox of biocatalysts for chiral amine synthesis and therefore their scope and application is still very much being explored. The research carried out as part of this PhD is presented as a series of manuscripts that have either been published or are planned for submission to peer-reviewed journals. The choice of presenting this thesis in journal format was made because a considerable body of the candidate’s PhD research has been published, with the rest planned for publication in the near future. Furthermore, the compiled review articles and research papers lend themselves to a clear thesis narrative and, combined, have taken considerable time and effort to prepare, equal to that of a traditional thesis format. The contents are organised as follows: Chapter 1: an introduction to biocatalysis and its impact on sustainable chemical manufacturing; Chapter 2: a review assessing the current state of the art in imine reductase biocatalysts; Chapter 3: a perspective on the design and implementation of biocatalytic cascades; Chapter 4: a research article on the application of IREDs in a biocatalytic cascade for the synthesis of chiral piperidine and pyrrolidine frameworks; Chapter 5: aims of the PhD project; Chapter 6: a research article on the discovery and investigation of a reductive aminase (RedAm) found within the IRED family; Chapter 7: a research article on the screening of a diverse set of novel IREDs for their ability to facilitate reductive amination; Chapter 8: a research article on the synthesis of complex bulky dibenz[c,e]azepine compounds using IRED and transaminase biocatalysts; Chapter 9: a summary and outlook; Chapter 10: manuscript supporting information further detailing experimental work; Appendix: list of other publications resulting from this doctoral research.

Details

Original languageEnglish
Awarding Institution
Supervisors/Advisors
Award date1 Aug 2018