Universal Chemical Programming Language for Robotic Synthesis Reproducibility

Abstract The amount of chemical synthesis literature is growing quickly, but it still takes a long time to share and evaluate new processes because of cultural and practical barriers. Herein, 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 different hardware and in different laboratories. With around fifty 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, matching those achieved by an expert chemist. This allows for faster and more secure research workflows and can be used to increase the throughput of a process by number-up instead of scale-up. To achieve that we use Chemputer-type platforms at the University of Glasgow and the University of British Columbia, Vancouver as well as Opentrons- and multi-axis cobotic robots to distribute and reproduce experimental results. In total, protocols for 7 complex molecules were validated and disseminated to be reproduced in two international laboratories and on three independent robots.