Jones, A.B.; (2011) Studies towards combined chemo-biocatalytic reactions in water. Doctoral thesis , UCL (University College London).

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Abstract

In recent years green chemistry has been increasingly applied to industrial syntheses. One key area of growth is the use of biocatalysts to perform reactions selectively in non-organic media. However, there is currently no set development process for the discovery and evolution of enzymes to be applied in these reactions. A process has been suggested by Hailes et al, part of which is the development of chemical reactions that work in combination with the biocatalysts.1 The interface between traditional chemistry and biocatalysis has yet to be fully explored, particularly in relation to the potential degree of interaction between the two synthetic techniques. The development of a chemical reaction that can be used in one-pot with a biotransformation is explored within this thesis. The synthesis of a standard to calibrate an assay of the transketolase selectivity was performed first. This allowed the stereochemistry of the starting material of the reductive amination being developed to be determined. Next a reductive amination reaction that proceeded in water and in the presence of transketolase was discovered and then optimized using cyclohexanone as a test substrate. This reaction was developed so that it could offer an alternative to a similar transformation performed by a transaminase enzyme, specifically with respect to substrate and stereoselectivity. This optimized reaction was then applied to an intermediate (1,3-dihydroxy-pentan-2- one), synthesized both using standard organocatalytic techniques and a biotransformation using transketolase, to produce 2-benzylamino-pentane-1,3-diol. The reaction was seen to be diastereoselective and an alternative transfer hydrogenation reaction that displayed the opposite selectivity was also investigated. This complimentary pair of reactions meant that all four diastereoisomers of 2-benzylamino-pentane-1,3-diol could potentially be synthesized. This work illustrated that the development of chemical reactions towards one-pot cascade reactions with biocatalysts is possible.

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