Advancing, enabling and democratizing chemical synthesis

A new automated, remotely accessible platform allows single- and multistep synthesis without requiring physical manipulation of the instrument between processes. Max-Planck Institute scientists in Germany achieve breakthrough

March 18, 2020
The radial synthesizer arranges different reaction conditions around the central station, and solutions can make round-trips through these conditions to perform the desired chemistry – much like trains from a central station

Advancing and automating chemical synthesis
The development of a new automated synthesizer opens up new avenues for chemical research and production by enabling scientists to carry out experiments remotely. Unlike other automated reactors, the new apparatus doesn´t need any reconfiguration when switching between different processes. It is capable of single and multistep synthesis via infinite synthetic routes exploiting a new paradigm called radial synthesis – developed by chemists from the Max Planck Institute of Colloid and Interfaces.

This new technology not only has the extraordinary potential of facilitating chemical production in areas with limited infrastructure, but also enables the expansion of chemical data sciences by removing both the source of error due to manual operation and the requirement of having skilled organic chemists to perform reactions.

Chemical production is made to measure. Regardless if it is an active pharmaceutical ingredient or other chemical product, bespoke processes are mirrored by the corresponding equipment, whose arrangement is specifically dedicated to one product. That could be much easier in the future - at least if a substance is not used in huge quantities – thanks to the radial synthesizer.

"We are creating a paradigm shift in chemistry," says Prof. Peter Seeberger, director at the Max Planck Institute of Colloid and Interfaces

Global access to standardized, advanced technology
This new instrument brings us a step further towards the next phase of how research can be performed. Currently, researchers are limited by the technology they have access to – which is why cheap, multipurpose round bottom flasks are found in laboratories worldwide. However, human error and the difficulties of performing sensitive reactions in flasks have led to a reproducibility crisis in chemistry. While several automated synthesis platforms exist – they do so in isolation in well-funded laboratories and require skilled users to reconfigure the systems for each new synthesis.

The radial synthesizer is preconfigured to be able to run any single-, multistep, or library synthesis without requiring flow chemistry expertise or physical manipulation of the system. Combined with a fully automated platform, the system can be accessed and used for any flow chemical synthesis without the need to be physically present. This means that any chemist, regardless of location and local resources, can utilize state-of-the-art technology for their research – democratizing technological advances.

Enabling chemists and data sciences
“By removing the need to physically set-up and run experiments, we free up chemists to devote their creativity to interpreting results and planning next steps” says Dr. Kerry Gilmore, leader of the project at the Max Planck Institute for Colloids and Interfaces.

"This also allows the broader community to collect more reliable data" says Seeberger. That, in turn, could contribute to the advances of big data analysis in chemistry. "And ultimately, even an artificial intelligence that has developed chemical competence through training with the large amounts of data could take over the search for promising new substances for a desired application or for efficient reaction paths," says Seeberger.

How it works
The radial synthesizer combines two fundamentally different approaches to synthesis, taking the versatility achieved in linear small molecule syntheses and the lack of equipment redundancy in biopolymer synthesizers. Much like destinations from a central train station, variable reaction conditions (heated reactors, photoreactors, etc.) are equally accessible for round-trip passage to perform the desired reaction. Upon returning to the central hub, the next destination (set of conditions) can be chosen and immediately accessed. Analytic equipment incorporated into the instrument allow researchers to monitor and quantify efficiencies after each step. This sequential, non-simultaneous approach allows for a significant increase in the versatility of each step without requiring new equipment each time.

In addition to being remotely accessible, the system is comprised completely of commercially available equipment, and the researchers have made the complete software to control and operate the synthesizer freely available to any academic researcher.

Availability
The software with detailed instructions for its use, pictures, videos, and summaries are freely available to any academic researcher at synthesizer.mpikg.mpg.de.

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