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Novel Biomimetic Organocatalysts

Objective

The primary aim of this project is to substantially expand the frontiers of current benchmark organocatalytic technology by the design, preparation and evaluation of the first class of thiol-based nucleophilic catalyst capable of emulating the action of NAD+-dependant enzymes such as aldehyde dehydrogenases, which promote the chemoselective oxidation/reduction of aldehyde substrates under mild conditions in aqueous media. The proposed artificial enzymes are designed biomimetically (in the true sense of the word) – only careful examination of the core enzyme competencies, modes-of-action and active sites has guided the design process. One of the key issues which this proposal addresses is the inherent difficulty associated with the design of artificial cofactor-dependent enzymes due to the requirement for a) efficient recognition by the catalyst of both the substrate and the cofactor, and b) the exertion of control over their encounter in the active site. We intend to tackle this challenge by covalently attaching groups functionally equivalent to the catalytically active residues of aldehyde dehydrogenases to a rigid NAD+ analogue in a manner which allows for their synergistic and biomimetic cooperation. Structure determination/mechanistic studies and the application of these new catalysts in a range of oxidations/reductions (we envisage that this project will result in the first organocatalyst able to demonstrably promote either - depending on the reaction conditions), (dynamic) kinetic resolutions, desymmetrisations, and ligations) will be undertaken and the development of catalytic processes for reactions currently outside the scope of any catalytic methodology is a clear long-term goal. We also wish to pursue the application of this potentially groundbreaking nucleophilic catalytic technology (for which no efficient organocatalysts have been thus far reported) toward the selective synthesis of enantiopure building blocks and pharmaceutically relevant molecules.

Field of science

  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins/enzymes

Call for proposal

ERC-2007-StG
See other projects for this call

Funding Scheme

ERC-SG - ERC Starting Grant

Host institution

THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN
Address
College Green
2 Dublin
Ireland
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 249 772
Principal investigator
Stephen Connon (Prof.)
Administrative Contact
Deirdre Savage (Ms.)

Beneficiaries (1)

THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN
Ireland
EU contribution
€ 1 249 772
Address
College Green
2 Dublin
Activity type
Higher or Secondary Education Establishments
Principal investigator
Stephen Connon (Prof.)
Administrative Contact
Deirdre Savage (Ms.)