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Development of enzymatic methods for the synthesis of enantiopure volatile sulfur compounds

Student thesis: Doctoral ThesisDoctor of Philosophy

Enantiopure sulfur compounds are desirable in a wide range of applications in pharmaceutical, organic and fragrance industries. Volatile sulfur compounds (VSCs) contribute to the distinctive flavours of many foods. Interestingly, the epimers of chiral VSCs often lead to different sensory properties and potencies. Enantiopure VSCs are difficult to synthesise and present in too low a concentration in foods to be efficiently extracted. Since VSCs are also labile and volatile, high selectivity under mild conditions are essential for their isolation. Biocatalysts, enzymatic material used to catalyse synthetic organic reactions, are thus an attractive means of synthesising enantiopure sulfur compounds. The aim of this project was to develop biocatalytic methods to yield a range of enantiopure sulfur compounds possessing a stereocentre on either the C-S or C-OH groups, Figure 1-1. Suitable analogues were designed and synthesised using chemical synthetic methods, and panels of ketoreductases (KREDs), nitrilases, and monoamine oxidases from Aspergillus niger (MAO-N) were then screened using colorimetric, spectrophotometric and small-scale reactions to assess their ability to biotransform these substrates. KREDs were employed for the synthesis of enantiopure 1,3- and 1,2-mercaptoalkanols. Methods to facilitate both stereoselective reductions of prochiral ketones with a chiral C-OH moiety, and dynamic kinetic resolutions of racemic aldehydes bearing a C-S stereocentre in alpha position, were developed. A dynamic kinetic resolution of a range of α-mercaptoacids from the α-mercaptonitrile was also demonstrated using nitrilases. Lastly, a novel multicomponent reaction to yield 1,2-mercaptoamines is described, which are then treated with MAO-N. Methods have been developed which demonstrate a promising and mild means of yielding enantioenriched sulfur compounds with chirality on both the C-S and C-OH centres.
Original languageEnglish
Awarding Institution
Supervisors/Advisors
Award date1 May 2020

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