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Universal chemical programming language for robotic synthesis repeatability

  • Robert Rauschen,
  • Mason Guy,
  • Jason E. Hein,
  • Leroy Cronin

摘要

The amount of chemical synthesis literature is growing quickly; however, it takes a long time to share and evaluate new processes among laboratories. Here we present an approach that uses a universal chemical programming language (χDL) to encode and execute synthesis procedures for a variety of chemical reactions, including reductive amination, ring formation, esterification, carbon–carbon bond formation and amide coupling on four different hardware systems in two laboratories. With around 50 lines of code per reaction, our approach uses abstraction to efficiently compress chemical protocols. Our different robotic platforms consistently produce the expected synthesis with yields up to 90% per step, allowing faster and more secure research workflows that can increase the throughput of a process by number-up instead of scale-up. Chemputer-type platforms at the University of Glasgow and the University of British Columbia Vancouver were used, as well as Opentrons robots and multi-axis cobotic robots to distribute and repeat experimental results. Protocols for three case studies involving seven reaction steps and three final compounds were validated and disseminated to be repeated in two international laboratories and on three independent robots.