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

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.