Project description
New steps to synthesising amino acids for pharmaceuticals
Non-natural amino acids are crucial for pharmaceuticals, such as the COVID-19 drug Paxlovid. However, synthesising non-natural isomers of amino acids with two chiral centres, such as isoleucine and threonine, remains challenging and is not commercially viable through current processes. The EIC-funded cassaFLOW project aims to develop a more efficient and scalable method for synthesising these amino acids. By shortening the existing synthesis process, the project plans to replace the current 8-step stereoselective synthesis with a streamlined 3-step cascade process. This new technology will convert long reaction pathways into shorter, cleaner processes, facilitating a 3-step synthesis of isoleucine. The project's outcomes will support the EU Strategic Autonomy 2013-2023 Plan and the Pharmaceutical Strategy for Europe.
Objective
Non-natural amino acids are essential building blocks for pharmaceuticals. The COVID-19 drug Paxlovid is a prime example for this. But as for most pharmaceuticals, the synthesis of these amino acids is complex and requires many steps. This is especially true for amino acids with 2 stereocenters, the focus of this application. Of the group of the 20 most common natural amino acids 2 have not one but two chiral centers: isoleucine and threonine. Non-natural isomers of these 2 amino acids are surprisingly difficult to make and commercially not available via an economically viable process. At the same time they are highly important for the production of drugs like Paxlovid.
In cassaFLOW, we will develop a cascade for the stereoselective synthesis of amino acids with 2 stereocenters. Based on the scalable breakthrough technology developed in our previous project ONE-FLOW, we will design cascades of reactions shortening the current syntheses. The main objective is to replace an 8-step stereoselective synthesis of an amino acid with a 3-step cascade to the same amino acid. This will be achieved by installing 2 stereocenters in 1 biocatalytic step and by applying flow technology from the ONE-FLOW project. Here, we will telescope long reaction paths with multiple work up steps into short and clean processes. Our innovative technology builds on ONE-FLOW methodology and will be combined with the reaction engineering and commercial expertise of the two SMEs in cassaFLOW, ChiralVision and SpinChem. The outcome of cassaFLOW will be a 3-step TRL 6 synthesis of an isoleucine that will replace the current 8-step production and can be directly placed on the market. Importantly, the cassaFLOW outcome will contribute to the EU Strategic Autonomy 2013-2023 Plan that aims to achieve a greater independence from delivery chains, and is in line with the Pharmaceutical Strategy for Europe that aims to produce pharmaceuticals with short production chains in Europe.
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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HORIZON.3.1 - The European Innovation Council (EIC)
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Call for proposal
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(opens in new window) HORIZON-EIC-2023-TRANSITION-01
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2628 CN Delft
Netherlands
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