Flexible flow synthesis of critical chiral medication

The current medical crisis provoked by SARS-CoV-2 has demonstrated that finding potential drugs and bioactive agents will not solve the problem alone. In order to make the therapies available to the crowds affected by the disease, it must also be possible to produce critical medication in large quantities as quickly as possible. Considering the severity of COVID-19 as well as the growing risk of similar pandemics, it would be necessary to establish novel manufacturing protocols that are sufficiently flexible to be utilized in various epidemiological challenges of the future. A chiral organic substance is carrying an asymmetric center and exhibits two non-superimposable isomers, called enantiomers. Although such isomers possess identical chemical and physical properties, they generally have markedly different biological effects. The overwhelming majority of drugs and bioactive agents holding potentials for COVID-19 and similar diseases bear one or more asymmetric centers and thus form isomers with differences in biological effects. The synthesis of enantiomerically pure drugs is therefore critical as concerns potent therapeutic strategies; however, such substances are significantly more difficult to synthesize, especially on a larger scale. These factors considerably contribute to the high costs of therapeutic medication and slow down its industrial production, which costs human lives during epidemiological crises. Inspired by these limitations, the project targets novel protocols for the rapid and sustainable synthesis of complex chiral substances which are potential as therapeutic agents against COVID-19 or which are vital in treatment of secondary medical implications provoked by harmful economic and societal effects of the crisis. To achieve these aims, the project will combine innovative catalyst design with continuous flow synthesis technology, which recently emerged as an enabling tool to simplify, integrate and scale-up chemical reactions. Unconventional activation modes of non-reactive substances are pivotal elements for accelerating chemical synthesis under directives of step- economy. In this context, photochemical transformations, which rely on the utilization of light as practically inexhaustible energy source will also be implemented in the research. The projected photo-flow methodologies will act as key reactions and will ensure bases for the multistep syntheses of critical chiral medication and related compounds. After investigation of individual reaction steps, synthesis of targeted substances will be achieved in uninterrupted flow assembly lines comprising asymmetric transformations as central elements, accompanied by diverse downstream reactions and real-time process monitoring by in-line analytical tools. Ultimately, we will establish flexible flow chemistry-based methodologies, which are capable of accelerating the production of difficult to access chiral medication essential to counteract current and future medical crises.

Considering the severity of COVID-19 as well as the growing risk of similar pandemics, it is necessary to establish novel manufacturing protocols that are sufficiently flexible to be utilized in various epidemiological challenges of the future. Importantly, it must also be possible to produce critical medication in large quantities as quickly as possible to make the therapies available to the crowds affected by the disease. A chiral organic substance contains an asymmetric carbon center and exhibits two non-superimposable isomers, called enantiomers. Although such isomers possess identical chemical and physical properties, they generally have markedly different biological effects. The overwhelming majority of drugs and bioactive agents holding potentials for COVID-19 and similar diseases bear one or more asymmetric centers and thus form isomers with differences in biological effects. The synthesis of enantiomerically pure drugs is therefore critical as concerns potent therapeutic strategies; however, such substances are significantly more difficult to synthesize, especially on a larger scale. These factors considerably contribute to the high costs of therapeutic medication and slow down its industrial production, which costs human lives during epidemiological crises. Inspired by these limitations, the project targeted novel protocols for the rapid and sustainable synthesis of complex chiral substances which are potential as therapeutic agents against COVID-19 or which are vital in treatment of secondary medical implications of the pandemic. To achieve these aims, the project combined innovative catalyst design with continuous flow synthesis technology, which emerged as an enabling tool to simplify, integrate and scale-up chemical reactions. Unconventional activation modes of non-reactive substances are pivotal elements for accelerating chemical synthesis under directives of step-economy. In this context, photochemical transformations, which rely on the utilization of light as practically inexhaustible energy source, were also implemented in the research. Selected photo-flow methodologies acted as key reactions ensuring bases for multistep syntheses of critical chiral medication and related compounds. Having explored individual reaction steps, the synthesis of targeted substances was achieved in uninterrupted flow assembly lines comprising asymmetric transformations as central elements, accompanied by diverse downstream reactions. Ultimately, we established flow chemistry-based flexible methodologies, which are capable of accelerating the production of difficult to access chiral medication essential to counteract current and future medical crises.