cassaFLOW · Cascades for Stereoselective Synthesis of Amino Acids

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.