Synthesis of many different types of organic small molecules using one automated process

Abstract

Small molecule synthesis usually relies on procedures 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 Csp3-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.

Iterative reactions of transient boronic acids enable sequential C–C bond formation

“…1 The ability to form multiple C-C bonds using iterative or one-pot methods allows a rapid increase in molecular complexity. [2][3][4][5] While many such sequences are known, there is still room to exploit new reactivity patterns and different chemical combinations derived from reactive intermediates. 6 In recent times, transition metal chemistry has dominated C-C bond cross-coupling strategies.…”

“…Due to the broad utility of boronic acids as starting materials in a number of key transformations, this approach could open up opportunities for new iterative C-C bond forming events which complement other elegant approaches. 2,3,[22][23][24][25][26] Figure 1|Prior work on boronic acids-diazo coupling and development of an iterative reaction strategy. a) Proposed mechanism for the combination of diazo species and boronic acids, followed by either protodeboronation and oxidation (previous work), or exploration of new reactivity of transient boronic acid species; b) mechanistic description for the sequential generation of the single addition product 3a and the double addition and generation of the corresponding products 5a1 and 6a1 via subsequent trapping with pinacol; c) setup for the generation, storage and reaction of the diazo species with boronic acids under full machine assistance (description of the setup can be found within the Supporting Information).…”

Chemistry: Why synthesize?

“…As a result we have lucrative peptide and oligonucleotide drugs, and glyco protein drugs are on the way. Work 9 by Martin Burke at the University of Illinois at Urbana-Champaign suggests that a great variety of small and medium-sized organic molecules could be made this way too.…”

Predicting the Performance of Organic Corrosion Inhibitors

“…Small organic compounds show promise as corrosion inhibitors, although their mechanisms of action are far from clear. Recent developments in automated high-throughput chemical synthesis [2,3], the availability of large libraries of organic compounds, high-throughput methods of assessing corrosion inhibition by mass loss, electrochemistry or other means, and the rapid growth in the capabilities of machine learning methods such as deep learning provide an unprecedented opportunity to discover or design new, more effective corrosion inhibitors [4,5]. Small molecule, synthetically accessible space is also vast, estimated to be~10 100 , providing rich opportunities for discovery of novel, effective small molecule corrosion inhibitors [6].…”