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An autonomous portable platform for universal chemical synthesis


Robotic systems for synthetic chemistry are becoming more common, but they are expensive, fixed to a narrow set of reactions, and must be used within a complex laboratory environment. A portable system that could synthesize known molecules anywhere, on demand, and in a fully automated way, could revolutionize access to important molecules. Here we present a portable suitcase-sized chemical synthesis platform containing all the modules required for synthesis and purification. The system uses a chemical programming language coupled to a digital reactor generator to produce reactors and executable protocols based on text-based literature syntheses. Simultaneously, the platform generates a reaction pressure fingerprint, used to monitor processes within the reactors and remotely perform a protocol quality control. We demonstrate the system by synthesizing five small organic molecules, four oligopeptides and four oligonucleotides, in good yields and purities, with a total of 24,936 base steps executed over 329 h of platform runtime.

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Fig. 1: Schematic representation of any synthesis carried out in the compact/portable platform.
Fig. 2: Summary of the implemented reaction and platform operations.
Fig. 3: Physical implementation of the portable platform.
Fig. 4: Synthetic schemes of five different APIs prepared using the platform.
Fig. 5: Fingerprinting and validation of phenelzine sulfate synthesis using the pressure profile.
Fig. 6: Schematic representation of the oligopeptides and oligonucleotides synthesized in the platform.

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Data availability

The Supplementary Information includes full details to reproduce this work. This consists of full details to reproduce the electronic and mechanical construction of the platform. The XDL files (.xdl), along with the respective graph (.json) and 3D reactor design (.stl), and full analytical data are provided, including our pneumatic fingerprint for the reactions, at

Code availability

Code is available from


  1. Nicolaou, K. C. & Jamir, S. C. Classics in Total Synthesis III: Further Targets, Strategies, Methods (Wiley, 2011).

  2. Nicolaou, K. C. & Sorensen, E. J. Classics in Total Synthesis: Targets, Strategies, Methods (Wiley, 1996).

  3. Nicolaou, K. C. & Snyder, S. A. Classics in Total Synthesis II: More Targets, Strategies, Methods (Wiley, 2003).

  4. Mehr, S. H. M., Craven, M., Leonov, A. I., Keenan, G. & Cronin, L. A universal system for digitization and automatic execution of the chemical synthesis literature. Science 370, 101–108 (2020).

    Article  CAS  PubMed  Google Scholar 

  5. Li, J. et al. Synthesis of many different types of organic small molecules using one automated process. Science 347, 1221–1226 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Steiner, S. et al. Organic synthesis in a modular robotic system driven by a chemical programming language. Science 363, eaav2211 (2019).

    Article  CAS  PubMed  Google Scholar 

  7. Angelone, D. et al. Convergence of multiple synthetic paradigms in a universally programmable chemical synthesis machine. Nat. Chem. 13, 63–69 (2021).

    Article  CAS  PubMed  Google Scholar 

  8. Coley, C. W. et al. A robotic platform for flow synthesis of organic compounds informed by AI planning. Science 365, eaax1566 (2019).

    Article  CAS  PubMed  Google Scholar 

  9. Merrifield, R. B. Automated synthesis of peptides. Science 150, 178–185 (1965).

    Article  CAS  PubMed  Google Scholar 

  10. Alvarado-Urbina, G. et al. Automated synthesis of gene fragments. Science 214, 270–274 (1981).

    Article  CAS  PubMed  Google Scholar 

  11. Plante, O. J., Palmacci, E. R. & Seeberger, P. H. Automated solid-phase synthesis of oligosaccharides. Science 291, 1523–1527 (2001).

    Article  CAS  PubMed  Google Scholar 

  12. Joseph, A. A., Pardo-Vargas, A. & Seeberger, P. H. Total synthesis of polysaccharides by automated glycan assembly. J. Am. Chem. Soc. 142, 8561–8564 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Jiang, T. et al. An integrated console for capsule-based, automated organic synthesis. Chem. Sci 12, 6977–6982 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Ley, S. V. & Baxendale, I. R. New tools and concepts for modern organic synthesis. Nat. Rev. Drug Discov. 1, 573–586 (2002).

    Article  CAS  PubMed  Google Scholar 

  15. Schotten, C., Leist, L. G. T., Semrau, A. L. & Browne, D. L. A machine-assisted approach for the preparation of follow-on pharmaceutical compound libraries. React. Chem. Eng. 3, 210–215 (2018).

    Article  CAS  Google Scholar 

  16. Chatterjee, S., Guidi, M., Seeberger, P. H. & Gilmore, K. Automated radial synthesis of organic molecules. Nature 579, 379–384 (2020).

    Article  CAS  PubMed  Google Scholar 

  17. Britton, J. & Jamison, T. F. A unified continuous flow assembly-line synthesis of highly substituted pyrazoles and pyrazolines. Angew. Chem. Int. Ed. 56, 8823–8827 (2017).

    Article  CAS  Google Scholar 

  18. Bédard, A.-C. et al. Reconfigurable system for automated optimization of diverse chemical reactions. Science 361, 1220–1225 (2018).

    Article  PubMed  Google Scholar 

  19. Ghislieri, D., Gilmore, K. & Seeberger, P. H. Chemical assembly systems: layered control for divergent, continuous, multistep syntheses of active pharmaceutical ingredients. Angew. Chem. Int. Ed. 54, 678–682 (2015).

    CAS  Google Scholar 

  20. Zhang, P. et al. Advanced continuous flow platform for on-demand pharmaceutical manufacturing. Chem. Eur. J. 24, 2776–2784 (2018).

    Article  CAS  PubMed  Google Scholar 

  21. Hou, W. et al. Automatic generation of 3D-Printed reactionware for chemical synthesis digitization using ChemSCAD. ACS Cent. Sci. 7, 212–218 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Kitson, P. J. et al. Digitization of multistep organic synthesis in reactionware for on-demand pharmaceuticals. Science 359, 314–319 (2018).

    Article  CAS  PubMed  Google Scholar 

  23. Zalesskiy, S. S., Kitson, P. J., Frei, P., Bubliauskas, A. & Cronin, L. 3D designed and printed chemical generators for on demand reagent synthesis. Nat. Commun. 10, 5496 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Agnew, P. C. et al. A clinical evalutation of four antidepresant drugs. Am. J. Psychiatry 118, 160–162 (1961).

    Article  CAS  PubMed  Google Scholar 

  25. Youatt, J. A review of the action of isoniazid. Am. Rev. Respir. Dis. 99, 729–749 (1969).

    CAS  PubMed  Google Scholar 

  26. Timmins, G. S. & Deretic, V. Mechanisms of action of isoniazid. Mol. Microbiol. 62, 1220–1227 (2006).

    Article  CAS  PubMed  Google Scholar 

  27. Zhang, Y., Dhandayuthapani, S. & Deretic, V. Molecular basis for the exquisite sensitivity of Mycobacterium tuberculosis to isoniazid. Proc. Natl Acad. Sci. USA 93, 13212–13216 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Heilmann, L., Wacker, J. & Rath, W. Diagnosis and treatment of hypertensive disorders during pregnancy in Germany: results of a survey in German obstetric clinics. Geburtshilfe Frauenheilkd 64, 589–599 (2004).

    Article  Google Scholar 

  29. Chakkath, T., Lavergne, S., Fan, T. M., Bunick, D. & Dirikolu, L. Alkylation and carbamylation effects of lomustine and its major metabolites and MGMT expression in canine cells. Vet. Sci. 2, 52–68 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Blaising, J., Polyak, S. J. & Pécheur, E.-I. Arbidol as a broad-spectrum antiviral: an update. Antivir. Res. 107, 84–94 (2014).

    Article  CAS  PubMed  Google Scholar 

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We thank D. Caramelli for producing the Supplementary Video and S. Rohrbach and M. Siauciulis for helpful comments on the manuscript. We gratefully acknowledge financial support from the EPSRC (grants nos. EP/L023652/1, EP/R020914/1, EP/S030603/1, EP/R01308X/1, EP/S017046/1 and EP/S019472/1), the ERC (project no. 670467 SMART-POM), the EC (project no. 766975 MADONNA) and DARPA (projects nos. W911NF-18-2-0036, W911NF-17-1-0316 and HR001119S0003). 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.

Author information

Authors and Affiliations



L.C. invented the concept and devised the project and the digitization approach, with help from J.S.M., S.S.Z. and P.J.K. S.S.Z. developed the initial system design and built the first prototype together with J.S.M. W.H. carried out reactionware synthetic routes for the small organic molecules, and P.F. and H.W. helped with method development for the synthesis of oligopeptides and oligonucleotides. J.S.M. carried out all the automated synthesis and developed the necessary code for the platform. J.S.M. and P.J.K. wrote the paper, with help from L.C.

Corresponding author

Correspondence to Leroy Cronin.

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Competing interests

The work described here has been filed as a patent GB 2213747.5 filed by the University of Glasgow.

Peer review

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Nature Chemistry thanks Melodie Christensen, Kerry Gilmore and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary Figs. 1–44, Tables 115, building instructions, methods, results and discussions.

Supplementary Video 1

Animation of a typical literature to cartridge to synthesis process.

Supplementary Data 1

stl, .xdl, .json for all the syntheses executed in the portable platform.

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Manzano, J.S., Hou, W., Zalesskiy, S.S. et al. An autonomous portable platform for universal chemical synthesis. Nat. Chem. 14, 1311–1318 (2022).

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