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New Horizons in C–H Activation: the ‘Real-World Molecules’ Challenge

Project description

Catalysts with 'kid gloves' gently replace hydrogen with delicate bioactive entities

Pharmaceuticals improve life expectancy, quality of life and health outcomes for countless conditions and diseases, yet their development is struggling to realise its full potential. This is in large part due to the characteristics of the ubiquitous, essential yet hard-to-break carbon–hydrogen (C–H) bond. Pulling hydrogens off bioactive molecules and replacing them with functional entities requires harsh reaction conditions unsuitable for the "survival" of many of these functional groups. The EU-funded RuCat project has the key to unlock the door to functionalisations not previously possible thanks to its exceptional new catalysts for C–H activation.

Objective

A 2018 joint report from pharma identified organic synthesis as one of the major bottlenecks in drug discovery today. In the highly competitive discovery environments, only fast-to-synthesise molecules are targeted, based mostly on five well-tested and proven synthetic methods. This approach has led to only a small portion of the chemical shape space being explored over the last decades and has been partly blamed for the recent low success rates in new drug development. The report emphasises the need for ideal tools such as late stage functionalisation, which would allow simply replacing any C‒H bond in a bioactive molecule with any desired functionality, thus greatly accelerating the synthesis of new candidates from a lead compound. However, the field of C‒H activation is significantly behind in achieving this aim: most biologically active molecules contain several polar and/or delicate functionalities (‘real world’ molecules), whereas most C‒H activation methods use harsh conditions, incompatible with delicate groups, and catalysts that tend to poison in the presence of polar groups.

This ERC Advanced Grant addresses this major challenge by building a new tool-set of ruthenium catalysts that will finally be able to deliver late stage functionalisation on ‘real world’ molecules, thus allowing a new dawn for development not only of new drugs, but also of agrochemicals, aromatic based organic materials and associated areas. The project builds on a recent key mechanistic breakthrough by the PI's group on the operation of Ru-catalysts (Nature Chemistry 2018) that reveals a completely different pathway to catalyst design from that followed in the field in the last two decades. This new class of catalysts presents unprecedented high reactivity and compatibility with sensitive ‘real world’ molecules. The PI is in a unique position to capitalize on this discovery and lead the way towards global late stage functionalisation of ‘real world’ molecules.

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Programme(s)

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Topic(s)

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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERC-ADG - Advanced Grant

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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) ERC-2018-ADG

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Host institution

THE UNIVERSITY OF MANCHESTER
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.

€ 2 498 959,00
Address
OXFORD ROAD
M13 9PL Manchester
United Kingdom

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Region
North West (England) Greater Manchester Manchester
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.

€ 2 498 960,00

Beneficiaries (1)

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