BioPhoCS · Bio- & Photo-Catalytic Methods for the Construction of Enantiomerically Pure C-S Bonds in Thiols and Sulphides
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2021-01-01 → 2023-05-31
- EU contribution
- €224,934
- Participants
- 2
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Bio- & Photo-Catalytic Methods for the Construction of Enantiomerically Pure C-S Bonds in Thiols and Sulphides
The chiral C–S bond is largely present in natural products and pharmaceutical agents, therefore, many methods have been developed for its asymmetric construction. However, the majority of the reported methods achieve the construction of chiral C–S bonds chemically, and there has been a surprising dearth of enzymatic approaches. The reported enzymatic methods for the assembly of chiral C–S bonds could be divided into two categories. (a) Microbial reduction of thioketones with baker's yeast carrying a complex enzyme system. However, except for the not easily accessible and unstable thioketones, poor yields for the desired thiols were obtained in all cases due to extensive and rapid hydrolysis of thioketones. Besides, although high stereoselectivities could be achieved in a few favourable cases, unsatisfactory enantioselectivities were observed in most cases. (b) Enzymatic kinetic resolution (KR) or dynamic kinetic resolution (DKR) of racemic C–S bonds, such as lipase-catalyzed KR of thioesters, 5-(hydroxymethyl)furfural oxidase (HMFO)-catalyzed KR of thiols, monoamine oxidase (MAO), nitrilase or ketoreductase (KRED)-catalyzed partial DKR of functionalized sulfides. Nevertheless, poor yields (<50% in KR) and moderate enantioselectivities were observed in most cases. The overall objectives of this project is to develop an efficient biocatalytic method for the construction of chiral C–S bonds, which will be able to addresses the long-standing issues faced in current enzymatic methods.
Data: CORDIS, © European Union
Project objective
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.
Original text from CORDIS.
Participants
- UNIVERSITY COLLEGE LONDON · LondonCoordinatorUnited Kingdom
- KING'S COLLEGE LONDON · LondonUnited Kingdom
Links
Data: CORDIS, © European Union