title: Synthesis of many different types of organic small molecules using one automated process.
abstract: Small-molecule synthesis usually relies on procedures that are highly customized for each target. A broadly applicable automated process could greatly increase the accessibility of this class of compounds to enable investigations of their practical potential. Here we report the synthesis of 14 distinct classes of small molecules using the same fully automated process. This was achieved by strategically expanding the scope of a building block-based synthesis platform to include even C(sp3)-rich polycyclic natural product frameworks and discovering a catch-and-release chromatographic purification protocol applicable to all of the corresponding intermediates. With thousands of compatible building blocks already commercially available, many small molecules are now accessible with this platform. More broadly, these findings illuminate an actionable roadmap to a more general and automated approach for small-molecule synthesis.
authors.affiliation: Howard Hughes Medical Institute (HHMI), Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Junqi
authors.initials: J
authors.lastname: Li
authors.affiliation: Howard Hughes Medical Institute (HHMI), Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Ballmer
authors.affiliation: Howard Hughes Medical Institute (HHMI), Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Gillis
authors.affiliation: Howard Hughes Medical Institute (HHMI), Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Seiko
authors.initials: S
authors.lastname: Fujii
authors.affiliation: Howard Hughes Medical Institute (HHMI), Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Schmidt
authors.affiliation: Howard Hughes Medical Institute (HHMI), Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Andrea M E
authors.initials: AM
authors.lastname: Palazzolo
authors.affiliation: Howard Hughes Medical Institute (HHMI), Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Lehmann
authors.affiliation: Howard Hughes Medical Institute (HHMI), Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Greg F
authors.initials: GF
authors.lastname: Morehouse
authors.affiliation: Howard Hughes Medical Institute (HHMI), Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. mdburke@illinois.edu.
authors.forename: Martin D
authors.initials: MD
authors.lastname: Burke
mesh_terms: D001331:Automation; D001897:Boronic Acids / Q000737:chemistry; D060326:Chemistry Techniques, Synthetic / Q000295:instrumentation / Q000379:methods*; D003500:Cyclization; D015394:Molecular Structure; D009930:Organic Chemicals / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification
chemical_list: D001897:Boronic Acids; D009930:Organic Chemicals