Bio- & photo-catalytic methods for the construction of enantiomerically  pure c-s bonds in thiols and sulphides
Organic sulphur compounds containing C-S chiral centres represent one of the most intriguing classes of chemicals due to their peculiar properties conferred by the unique chemistry of sulphur. Chiral sulphur compounds are known for their olfactory properties as flavours and fragrances and are ubiquitous in natural products and pharmaceutical ingredients such as penicillins and verticillins. Both the flavouring and pharmaceutical properties of chiral sulphur compounds are often determined by their absolute configurations. Therefore, the development of novel, robust and sustainable methods for the enantioselective construction of C-S bonds is of great importance in chemistry. In view of the lack of efficient and stereoselective methods in assembling asymmetrical C-S bonds, within this project we aim to construct enantiopure sulphur compounds through photo- and bio-catalysis. Various strategies have been designed to achieve this target, exploiting blue/green light photocatalysis and biocatalysis by reductase enzymes such as KRED, ADH and ERED. The ability of these enzymes to biocatalyse the enantioselective reduction of thioketones and thioalkenes obtained via photocatalysis, will be investigated. In addition, the combination of photocatalytic synthesis of substrates with the biocatalytic construction of enantiomerically pure C-S bonds in one-pot cascade processes will be developed. These methods will be finally applied to the synthesis of chiral volatile sulphur compounds as odorous excipients, while in-situ NMR kinetic studies of the photo-biocatalytic reactions will be carried out to get a better understanding of the reaction mechanisms. The successful development of these strategies will allow chemists and industries to access facile and sustainable approaches to prepare a wide range of challenging chiral thiols and sulphides to be used in the manufacturing of pharmaceutical ingredients, fine chemical tools (ligands, catalysts), agrochemicals and fragrances.