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Workstream (App) “F” – Enzymes in Flow/ Continuous Flow Synthesis of Chiral Amines

Worksteam Leader

Simon Dolan, GSK

Work Stream Objectives                                                                                              

The aim of this proposal is to start to look closely at the technical issues and economics of scale up in flow, baselined against the batch equivalent.

Strands summary                                                              

Explore the factors affecting conversion rates in flow for selected substrates of industrial relevance (one from each of GSK, AZ) and a more generic set of amine compounds to gauge the breadth of utility. Factors are: maintaining amine donor concentrations throughout the column, alternative amine donors to IPM, impact of residual water content and nature of solvent composition

Assess the impact of catalyst performance on the above by using different biocatalysts and immobilization strategies

Determine the stability of the catalysts and performance with time in the reaction media and impact on reaction rate.

Examine use of different flow systems – Plug Flow, CSTR, Multi-stage (e.g. Coflore) advantages/disadvantages

Investigation of isolation/purification process to enable a complete process for delivering chiral amines. Includes the removal of acetone to drive equilibrium (e.g. via wipe film evaporation)

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