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Development of a general strategy for the conversion of pyridines into benzonitriles

Project description

New method for converting pyridines into benzonitriles

Bioisosteric replacement is a key strategy in drug discovery, but replacing core ring structures usually requires de novo synthesis. Converting pyridines to benzonitriles is desirable, as benzonitriles exhibit properties similar to those of pyridines. However, current methods are limited. Supported by the Marie Skłodowska-Curie Actions programme, the DEPYR project will develop a new method for converting pyridines into benzonitriles in three steps: pyridine N-oxidation, photochemical deconstruction into a linear diene, and Diels-Alder cycloaddition to form the aromatic benzonitrile. This strategy offers a versatile platform for diversifying high-value pyridine products and provides a novel approach for synthesising complex benzonitriles. It aligns with the Leonori group’s use of photochemistry to modify aromatic structures. The project offers a new route to complex benzonitriles.

Objective

Bioisosteric replacement is crucial to drug discovery. However, substituting a central core ring structure generally requires de novo synthetic sequences due to the lack of “ring-replacing” strategies that can be used at a late-stage.

This project will focus on finding a solution to the challenge of converting pyridines into benzonitriles. This is a desirable “ring replacement” in medicinal chemist and benzonitriles can mimic pyridines' properties and are effective bioisosteres. However, current methods to convert pyridines to benzonitriles are limited to de novo synthetic approaches.

This project seeks to develop a novel strategy converting pyridines into benzonitriles. This will be achieved in just three steps by (1) pyridine N-oxidation, followed by (2) photochemical deconstruction into a nitrile-containing linear diene, which (3) is primed for Diels-Alder cycloaddition to reconstruct the aromatic benzonitrile.

This strategy will constitute a divergent platform for the diversification of high-value pyridine products and also a novel retrosynthetic tactic for the reparation of complex benzonitriles.

This research squarely fits within a recent new research direction the Leonori group where photochemistry is used to alter the structure of aromatic molecules.

The completion of such an innovative and ambitious project at RWTH Aachen University will be facilitated by generating, transferring, sharing and disseminating knowledge, and will enhance the Researcher future career following the training plan envisioned.

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

RHEINISCH-WESTFAELISCHE TECHNISCHE HOCHSCHULE AACHEN
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 202 125,12
Address
TEMPLERGRABEN 55
52062 Aachen
Germany

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Region
Nordrhein-Westfalen Köln Städteregion Aachen
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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