A Biocatalytic Platform for the Reduction of alpha,beta-Unsaturated Imines

  • Thomas Thorpe

Student thesis: Phd


Chiral amines are ubiquitous in valuable molecules, such as synthetic catalysts, agrochemicals and pharmaceuticals. Biocatalysis has become well established for the synthesis of primary amines and many enzyme classes are able to prepare these species efficiently. However, many important molecules contain secondary and tertiary amines and therefore the development of direct enzymatic methods for their synthesis is desirable. The biocatalytic conjugate reduction of activated alkenes is a convenient method for forming versatile intermediates for further enzymatic reactions. However, prior to this work no general biocatalysts had been identified for the conjugate reduction of alpha,beta-unsaturated C=N bonds (ene-imines/iminiums), a reaction that would form useful precursors for the synthesis of secondary and tertiary amines. In this thesis, ene-reductases and imine reductases have been identified for the asymmetric reduction of ene-imines/iminiums. These enzymes were employed in three synthetic applications: i) the asymmetric full reduction of cyclic ene-imines, ii) the stereoselective conjugate reduction reductive amination of alpha,beta-unsaturated carbonyls, and iii) the asymmetric chemo-enzymatic dearomatisation of activated pyridines. Through these new synthetic methods a broad selection of stereoenriched secondary and tertiary amines could be prepared, including bioactive molecules and their precursors. Furthermore, the mechanism of conjugate reduction was investigated for ene-reductases and imine reductases, revealing a different intermediate for each. The identification of members of two industrially viable enzyme families that can catalyse CR of alpha,beta-unsaturated C=N bonds offers a platform for the development of further applications in synthesis.
Date of Award1 Aug 2022
Original languageEnglish
Awarding Institution
  • The University of Manchester
SupervisorSabine Flitsch (Supervisor) & Nicholas Turner (Supervisor)


  • redox reactions
  • asymmetric catalysis
  • biocatalysis

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