Although the automatic synthesis of molecules has been established, each reaction class uses bespoke hardware. This means that the connection of multi-step syntheses in a single machine to run many different protocols and reactions is not possible, as manual intervention is required. Here we show how the Chemputer synthesis robot can be programmed to perform many different reactions, including solid-phase peptide synthesis, iterative cross-coupling and accessing reactive, unstable diazirines in a single, unified system with high yields and purity. Developing universal and modular hardware that can be automated using one software system makes a wide variety of batch chemistry accessible. This is shown by our system, which performed around 8,500 operations while reusing only 22 distinct steps in 10 unique modules, with the code able to access 17 different reactions. We also demonstrate a complex convergent robotic synthesis of a peptide reacted with a diazirine—a process requiring 12 synthetic steps.
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All the data are available in the supplementary volume. This includes full experimental details to build the Chemputer as well as compound characterization.
The code to run the hardware for the automated platforms and the scripts to run the reactions are available in the supplementary volume and in the open-source repository (https://github.com/croningp/ChemputerConvergence).
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We thank BUCHI for supplying us with an R-300 rotary evaporator and an API to interface it with the Chemputer software package, D. Castro for help with the NHS-diazirine peptide synthesis and purity assessment, H. Mehr for Python advice on the conductivity sensor development and A. Jones for suggesting the diazirine synthesis challenge. We also thank M. Symes, P. Kitson and N. Bell for comments on the manuscript as well as N. A. B. Johnson for her artistic depiction of the Chemputer platform in the TOC graphic. We thank the following funders: EPSRC (Grant Nos. EP/H024107/1, EP/J00135X/1, EP/J015156/1, EP/K021966/1, EP/K023004/1, EP/L023652/1), ERC (project 670467 SMART-POM). This research was developed with funding from the Defense Advanced Research Projects Agency (DARPA). The views, opinions and/or findings expressed are those of the authors and should not be interpreted as representing the official views or policies of the Department of Defense or the US Government.
L.C. is the founder of DeepMatter Group PLC and Chemify Ltd., which aims to commercialize various aspects of the digitization of chemistry, including discovery and synthesis using universal robotic platforms.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Figs. 1–152, Tables 1–33, building instructions, methods, module test results and discussions.
Raw and processed NMR data.
STL files for all 3D printed parts.
DXF files for all laser cut parts.
Circuit schematics and firmware for all custom-made PCBs.
Various schematics for different Chemputer modules.
Python modules and scripts used to execute the automated syntheses.
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Angelone, D., Hammer, A.J.S., Rohrbach, S. et al. Convergence of multiple synthetic paradigms in a universally programmable chemical synthesis machine. Nat. Chem. 13, 63–69 (2021). https://doi.org/10.1038/s41557-020-00596-9
Journal of Materials Science (2021)