Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - One-Flow (Catalyst Cascade Reactions in ‘One-Flow’ within a Compartmentalized, Green-Solvent ‘Digital Synthesis Machinery’ – End-to-End Green Process Design for Pharmaceuticals)

Teaser

ONE-FLOW aims to create a technological equivalent of the biochemical assembly lines in nature. From a process engineering point of view this requires the adaptation of continuous processing conditions that allow the use of 1 solvent, 1 temperature, 1 pressure and fine-tuned...

Summary

ONE-FLOW aims to create a technological equivalent of the biochemical assembly lines in nature. From a process engineering point of view this requires the adaptation of continuous processing conditions that allow the use of 1 solvent, 1 temperature, 1 pressure and fine-tuned synthesis and control.
In order to achieve this overall aim ONE-FLOW explores the following enabling functions in step-wise and team-grouped fashion. First, orthogonality will be ‘forced’ by compartmentalization with Pickering Emulsions/Polymersomes and with switchable smart fluids. Then, orthogonality will be proactively enforced by optimized choice of reagents, solvents and conditions. Thereafter, the ONE-FLOW processing will be digitalized and transferred in a platform technology. Each of these central project objectives represents a tangible outcome of the project with value on its own.

WP1: ‘The Compartmentalized Smart Factory’ We will develop and introduce compartmentalization approaches for flow: (i) polymersomes composed of block copolymers – ‘Organic self-assembly’, (ii) Pickering emulsions stabilized by solid particles – ‘Inorganic self-assembly’, (iii) structured microfluidic multiphases – ‘Physical self-assembly’, and (iv) chemisorption-anchored catalysts – ‘Mechanical self-assembly’.
WP2: ‘The Green-Solvent Spaciant Factory’ Pharmacy likes to largely minimize use of non-green solvents and has banned the ones with largest environmental hamper. Our approach aims to ban such solvents completely, with the exception of a very few alcohols, water and functional green solvents. The latter allow to open and close interim reaction spaces alike reactors do, but more elegantly; thus, being named spaciants.
WP3: ‘The Systemic Operations Factory’ If full orthogonality is provided alike in the (bio )chemical assembly line, unit operations of chemical engineering virtually vanish to a systemic operation in the flow cascade. The ultimate level of harmonization will be such continuous “One-Flow” processing for which an engineering methodology is envisioned.
WP 4: ‘The Digital Machine-to-Machine Factory’ The “Internet of Chemical Things” is poised to alter the landscape of chemical synthesis, enabling simple machine-to-machine data transfer and relegation of process monitoring to central computer systems under the oversight of chemists.
WP5: ‘The Fully Continuous Integrated Factory’ To ensure right process selection and to avoid dead-end scenarios, a process-design evaluation is performed, using life-cycle assessment and cost analysis to monitor sustainability. In this way, a maximal impact between green chemistry and green engineering is enforced. This together with a ‘critical process parameter map’ will result in a foundation towards a commercial platform technology, i.e. the innovation leaves academic doors. This toolbox will make amenable the new kind of processing to all chemists.

The main importance for society is that ONE Flow leads to a radical new approach how complex molecules are made. It has the potential to change the face of the chemical industry, making it more sustainable and more effective in the development of molecules for especially the pharmaceutical industry

Work performed

The program has worked on the development of new synthetic routes toward 4 important classes of pharmaceutical compounds. This involves the compatibilization between chemo and biocatalysts using innovative approaches, such the use of polymeric nanoreactors, Pickering emulsions and smart solvent combinations.
This compatibilization strategy has already been successfully been applied for two of the three cascade reactions under investigation.
Furthermore, integrated flow devise have been developed which have allowed the fast optimization of a series of reactions involving boronic acid compounds. The platform allows the operation of the reactors from a distance, with minima; costs of chemicals and operation time.
The choice for the development of the right platform is furthermore streamlined for both the process conditions and equipment design. This will allow fast implementation of novel cascade processes into a flow-controlled operation system.
The research activities have led to the publication of 14 research papers. Furthermore a workshop has been organized and company contacts have been initiated. Via the ONE-Flow website we keep the general audience informed about the progress of the project.

Final results

The approach followed is fundamentally different than what has been done in the past in organic synthesis. The development of an automated flow device for reaction optimization and production, with minimal purification steps is a holy grail for the pharmaceutical industry. Already one example has been demonstrated in which the compound Rufinamide is produced according to this new philosophy. What we hope to achieve is that chemists will be more focused on the design of the molecules rather than having to spend most of their time in optimizing their syntheses. This will tremendously increase the innovative potential of the chemical industry, which will be a great profit for society as it will lead to a faster development of useful molecules such as pharmaceutical ingredients.

Website & more info

More info: https://one-flow.org/.