Fully Automated Chemical Synthesis: Toward the Universal Synthesizer

Abstract

Automated peptide and oligonucleotide synthesizers enabled a revolution in molecular biology and helped pave the way to modern synthetic biology. Similarly, fully automated synthetic chemistry could herald a new wave of innovation in biology and materials sciences by greatly facilitating access to known and novel molecules. Here, we report on an automated multistep chemical synthesizer, AutoSyn, that makes milligram-to-gram-scale amounts of virtually any drug-like small molecule in a matter of hours and demonstrate its versatility with the synthesis of ten known drugs. Of the FDA-approved small-molecule drugs for which we were able to compute a synthetic route, 87% are predicted to be synthesizable on AutoSyn. Moreover, AutoSyn enables digital synthesis protocols that ensure the reproducibility and transferability of synthesis protocols from one lab to another.