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Peptide-based Hydrogen Bonding Phase-Transfer Catalysis for Asymmetric Nucleophilic Fluorination

Project description

Peptide catalysts for drug development

The addition of fluorine atoms to molecules is a common procedure in pharmaceutical development as it improves the stability, potency, and the safety of drugs. However, creating fluorinated molecules in a controlled way remains a major challenge. With the support of the Marie Skłodowska-Curie Actions programme, the ANFPEP project aims to develop a new, simple method for adding fluorine using specially designed short peptides. Researchers will study how these peptides interact with simple fluoride salts and use this knowledge to guide the fluorination of useful building blocks for medicines. By improving and tailoring the peptide designs, the project is designed to provide chemists with a practical new tool for making high-value fluorinated compounds.

Objective

Asymmetric nucleophilic fluorination remains one of the most challenging transformations in organic chemistry. In light of the importance of chiral fluorochemicals for the pharmaceutical sector, the development of innovative enantioselective fluorination methods with alkali metal fluoride is highly desirable. In this work, we propose to merge two conceptual manifolds, namely peptide-based organocatalysis and hydrogen bonding phase-transfer catalysis. We propose to investigate experimentally the binding ability of an extensive β-turn-based peptide library to fluoride, a fundamental unprecedented study. The insight into the binding profiles and conformational properties of these peptides will be essential for developing an asymmetric catalytic nucleophilic fluorination procedure. In this context, we shall first focus on synthesising pharmaceutically relevant cyclic β-fluoroamines. Subsequently, the peptide-catalyst design will be further refined by introducing a substrate binding region for targeting aryl amides, esters, thioesters, and sulfones. Upon completion, this work will provide medicinal chemists with a novel peptide-catalysed asymmetric nucleophilic fluorination reaction, an advance expanding the scope of organocatalytic nucleophilic fluorination reactions.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

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

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Call for proposal

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

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Coordinator

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Net EU contribution
€ 260 347,92
Address
WELLINGTON SQUARE UNIVERSITY OFFICES
OX1 2JD Oxford
United Kingdom
Region
South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire
Activity type
Higher or Secondary Education Establishments
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Total cost
No data