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Rhodium-catalyzed carbyne transfer strategy to streamline synthesis of housane

Project description

A new method of housane production could transform drug design and medicinal chemistry

Cyclopropanes and cyclobutanes are small ring structures commonly used in drug molecules because they improve how drugs behave in the body. However, a unique structure that combines these two rings, called housane, has been largely unexplored mainly owing to the lack of efficient methods for its synthesis. With the support of the Marie Skłodowska-Curie Actions programme, the Housane project plans to develop a new method to construct housanes using a chemical process called Rh-catalysed carbyne transfer. The proposed approach will make it easier and more sustainable to create housanes, which could lead to new drug discoveries. Researchers will collaborate with a pharmaceutical company to test real-world applications.

Objective

Aliphatic sp3-rich ring systems such as cyclopropanes and cyclobutanes are commonly observed motif in drug molecules. This is due to the fact that they can positively influence metabolic stability, conformation, pKa, entropy, membrane permeability or pharmacokinetics in drug leads. However, the molecule consists of a cyclopropane fused to cyclobutane, traditionally known as ‘housane’ is significantly underexplored and yet to appear in drug molecules. This can largely be attributed to the lack of general synthetic methods for the preparation of this motif. Current protocols for the synthesis of housane, require multistep manipulations or pre-functionalized substrates, which means low efficiency and sustainability. Housane aims to develop an innovative technology to rapidly construct housanes and housane derivative of drug molecules from feedstock and fine alkenes based on a Rh-catalyzed carbyne transfer platform. A key strength of this conceptually new and multidisciplinary proposal is the introduction of a secondment phase in Janssen (Toledo, Spain) to explore real-life applications. The ambitious action merges perfectly with the expertise of the host in novel C-H and C–C bond functionalization strategies based on the catalytic generation of carbyne equivalents with the strong background of the applicant in transition metal-catalyzed asymmetric allylic substitution chemistry, thus enhancing two-way transfer of knowledge between the ER and the host group. This project will expose the fellow to a wide range of cutting-edge chemistry including medicinal chemistry in an interdisciplinary and international environment (ICIQ, Janssen) and enable the fellow to become a leader for the next generation in the field of organic synthesis, homogeneous catalysis and medicinal chemistry.

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

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Call for proposal

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

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Coordinator

FUNDACIO INSTITUT CATALA D'INVESTIGACIO QUIMICA
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.

€ 209 914,56
Address
AVENIDA PAISSOS CATALANS 16
43007 TARRAGONA
Spain

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Region
Este Cataluña Tarragona
Activity type
Research Organisations
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