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Molecular Editing by Nitrogen Insertion

Project description

Selective and mild nitrogen insertion techniques for molecular editing

Compounds containing nitrogen heterocycles account for nearly 60 % of all small molecule drugs. Although synthesis of such compounds is possible through nitrogen insertion, the method is quite inefficient owing to substrate limitations, harsh reaction conditions and unselective results. The ERC-funded NINSERT project aims to develop methods that will facilitate the synthesis of nitrogen containing compounds through selective and mild nitrogen insertion, largely focusing on heterocyclic motifs. To do so, it will leverage recent advances in late-stage skeletal editing, modifying physicochemical properties to develop reagents, design catalysts and assess synergistic impacts. Thus, NINSERT will provide a molecular editing platform with highly selective methods to allow pharmaceutical researchers to customise compound profiles for future drug development.

Objective

NINSERT constitutes a program to embark on selective and mild nitrogen insertions, both within and beyond carbonyl chemistry. Reagent development, catalyst design, and synergistic effects will be evaluated to provide a platform for late-stage skeletal editing, an area that has been recently brought to the forefront of organic chemistry. With a primary emphasis on heterocyclic motifs, commonly encountered in natural products and drug candidates, NINSERT offers a powerful tool to streamline future syntheses of nitrogen containing compounds. Notably, approximately 59% of all small-molecule drugs feature nitrogen heterocycles, underscoring the profound impact this program will have on pharmaceutical research. Adjusting physicochemical properties by late-stage nitrogen insertion will enable medicinal chemists to tailor the overall compound profile on its way to candidate-nomination and ultimately clinical studies. Furthermore, asymmetric methods, as elucidated in this proposal, will give rise to molecular complexity within the 3D chemical space. Guided by the principles of strain-release and molecular recognition, we will utilize our expertise on asymmetric ring expansion and atom insertion reactions to deliver highly selective methods applicable to both academic and industrial research. Despite the pioneering work of Beckmann and Schmidt over a century ago, nitrogen insertions have remained significantly constrained over the years, largely due to their substrate limitations, harsh reaction conditions, and unselective outcomes. The progression to selective and widely applicable nitrogen insertions has been long overdue and marks a major driving force behind the development of NINSERT.

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2024-STG

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Host institution

JOHANNES GUTENBERG-UNIVERSITAT MAINZ
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.

€ 1 462 500,00
Address
SAARSTRASSE 21
55122 MAINZ
Germany

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Region
Rheinland-Pfalz Rheinhessen-Pfalz Mainz, Kreisfreie Stadt
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.

€ 1 462 500,00

Beneficiaries (1)

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