PhotoArM · Directed Evolution of Photoredox Powered Artificial Metalloenzymes for Stereodivergent Catalysis
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2019-04-01 → 2021-03-31
- EU contribution
- €191,149
- Participants
- 1
- Scheme
- MSCA-IF
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Results in brief
Directed Evolution of Photoredox Powered Artificial Metalloenzymes for Stereodivergent Catalysis
This project aimed to address the need to find highly selective and sustainable methods of organic synthesis in order to access valuable chiral scaffolds. Complex molecules are often required for chemicals such as medicines with high levels of control needed to synthesise these correctly. This is to ensure they work as intended with high efficiency and without unwanted side effects that can be caused by different isomers of the same scaffold. Finding methods to access these directly in as few steps as possible reduces waste from separating and discarding the unwanted isomers. It is also important to be able to carry out the synthesis of compounds such as these sustainably to be environmentally conscious. By using non-valuable base metals and light to power the reaction this would provide a green approach to the synthesis and using a protein scaffold to control the selectivity should improve the efficiency of the reaction.
Data: CORDIS, © European Union
Project objective
Artificial metalloenzymes have recently emerged as powerful tools to address the ever-growing requirements of chemistry to become more efficient and sustainable. This methodology involves anchoring a reactive transition metal catalyst within a protein to exploit the secondary coordination sphere created around the new active site, which can induce selectivity in reactions and improve turnover numbers.Concomitantly, photoredox and metallophotoredox catalysis, where a small quantity of a light sensitive compound allows non-traditional reactivity though open shell reactive intermediates, has also developed dramatically in recent years. The impressive reaction repertoire is especially synthetically attractive due to the mild conditions required and the ability to activate abundant and generally more inert functional groups. However, the current drawback to this methodology is the high levels of control needed to give the reactions their full synthetic potential. This is where the two fields display complementarity with an unexplored interface: Photoredox Artificial Metalloenzymes.By anchoring a nickel catalyst inside an enzyme pocket with a nearby photocatalyst, it should be possible to control catalytic reactivity by mutagenesis of residues in the secondary coordination sphere. In the proposed case of an sp3-sp3 cross-coupling reaction between a racemic amino acid derivative and bromoalkane, this could potentially allow control over both new stereocentres independently to achieve stereodivergent catalysis. It is subsequently proposed that this methodology could be adapted to include intramolecular cross-coupling reactions, which would beneficially allow access to the valuable monocyclic β-lactam scaffold from suitably functionalised linear substrates. If possible, this may allow efficient access to diastereoisomers potentially difficult to access by other means, which may hold unexplored pharmaceutical potential.
Original text from CORDIS.
Participants
- UNIVERSITAT BASEL · BaselCoordinatorSwitzerland
Links
Data: CORDIS, © European Union