Convergence of multiple synthetic paradigms in a universally programmable chemical synthesis machine

Angelone, D., Hammer, A., Rohrbach, S. , Krambeck, S., Granda, J. M., Wolf, J., Zalesskiy, S., Chisholm, G. and Cronin, L. (2021) Convergence of multiple synthetic paradigms in a universally programmable chemical synthesis machine. Nature Chemistry, 13(1), pp. 63-69. (doi: 10.1038/s41557-020-00596-9) (PMID:33353971)

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Abstract

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Chisholm, Dr Greig and Angelone, Dr Davide and Zalesskiy, Dr Sergey and Rohrbach, Mr Simon and Granda, Dr Jaroslaw and Hammer, Mr Alexander and Cronin, Professor Lee and Wolf, Mr Jakob
Authors: Angelone, D., Hammer, A., Rohrbach, S., Krambeck, S., Granda, J. M., Wolf, J., Zalesskiy, S., Chisholm, G., and Cronin, L.
College/School:College of Science and Engineering > School of Chemistry
Journal Name:Nature Chemistry
Publisher:Nature Research
ISSN:1755-4330
ISSN (Online):1755-4349
Published Online:22 December 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Nature Chemistry 13(1): 63-69
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
190217Molecular-Metal-Oxide-nanoelectronicS (M-MOS): Achieving the Molecular LimitLeroy CroninEngineering and Physical Sciences Research Council (EPSRC)EP/H024107/1Chemistry
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190623The Multi-Corder: Poly-Sensor TechnologyDavid CummingEngineering and Physical Sciences Research Council (EPSRC)EP/K021966/1ENG - Electronics & Nanoscale Engineering
167864Energy and the Physical Sciences: Hydrogen Production using a Proton Electron BufferLeroy CroninEngineering and Physical Sciences Research Council (EPSRC)EP/K023004/1Chemistry
190796Programmable 'Digital' Synthesis for Discovery and Scale-up of Molecules, Clusters and NanomaterialsLeroy CroninEngineering and Physical Sciences Research Council (EPSRC)EP/L023652/1Chemistry
172151SMARTPOM: Artificial-Intelligence Driven Discovery and Synthesis of Polyoxometalate ClustersLeroy CroninEuropean Research Council (ERC)670467Chemistry