Bond-forming synthetic chemistry promoted by bacteria redox potential

Abstract

The development of non-natural, synthetic reactions that interact with the metabolism of living systems is an emerging field at the interface of chemical and biological synthesis. These reactions would give access to new sustainable synthetic routes for molecules of interest, and have potential applications in biomedicine and biology. In this Master dissertation, we demonstrate that the redox metabolism of live bacteria can be harnessed to promote non-natural bond-forming radical reactions. We show that the electrogenic bacterium Shewanella oneidensis MR‑1 and the model bacterium Escherichia coli DH5ɑ can reduce aryl diazonium salts to promote the Meerwein arylation of naphthoquinones using electron transfer and radical chain mechanisms. We have also tested our methodology for the bacteria-promoted synthesis of benzothiophenes, opening the door to structures of biomedical interest. This work was carried out in the Centro Singular de Química Biolóxica e Materiais Moleculares (CiQUS) of the University of Santiago de Compostela (USC) between September 2nd, 2024 and January 21st, 2025.