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Development of a Sustainable Bio-Organocatalytic Cascade for Stereoselective Amide Synthesis in Pharmaceutical Applications

Project description

Green chemistry platform for stereoselective amide synthesis

Many compounds can exist as stereoisomers – molecules with the same molecular formula and bonding arrangement but different 3D spatial configurations. This difference can significantly impact the molecule’s functionality, particularly in amide bond formation for the synthesis of many drugs containing amide. Thus, stereoselectivity to favour production of one of the isomers is very important. Current methods typically rely on harsh agents bad for the environment. With the support of the Marie Skłodowska-Curie Actions programme, the SuBStrAte project aims to develop a ‘green chemistry’ alternative. It will establish a process for direct transformation of carbonyl compounds into amides leveraging highly chemo-selective and stereoselective transaminases and a green catalyst in a sustainable bio-organocatalytic cascade.

Objective

Amide bond formation is fundamental to the synthesis of a wide array of amide-containing drugs. Conventional methods for amide synthesis typically rely on stoichiometric activating agents that are harmful to the environment and less sustainable. Therefore, there is an urgent need for more efficient, selective, and sustainable methods for amide synthesis. This project addresses these challenges by designing a novel bio-organocatalytic cascade reaction for the stereoselective synthesis of amides, including chiral amides, by integrating biocatalytic and organocatalytic strategies.
The proposed method exploits the high chemo- and stereoselectivity of ω-transaminases (ω-TAs) for the synthesis of chiral amines from carbonyl compounds, in conjunction with a newly developed direct amidation method using choline chloride (ChCl) as a green catalyst. This project will thus deliver an innovative platform for the direct transformation of carbonyl compounds into amides in a one-pot process. Adhering to green chemistry principles, the method eliminates the need for hazardous reagents and solvents, while employing mild reaction conditions and renewable catalytic systems. Additionally, microwave-assisted heating is utilized to accelerate the reaction rate, enhance yields, and reduce energy consumption. The bio-organocatalytic cascade will significantly reduce the number of steps, reaction time, and resource consumption compared to traditional methods. It will also be scaled up to demonstrate potential for industrial applications.
In summary, this interdisciplinary project combines expertise in biocatalysis, organocatalysis, microwave-assisted synthesis, and analytical chemistry to deliver a viable solution for sustainable amide synthesis, which is critical in pharmaceutical manufacturing.

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

UNIVERSITEIT VAN AMSTERDAM
Net EU contribution
€ 217 076,16
Total cost
No data