Nature Synthesis
Automation has fuelled dramatic advances in fields such as proteomics and genomics by enabling non-experts to prepare, test and analyse complex biological molecules, including proteins and nucleic acids. However, the field of automated organic synthesis lags far behind, partly because of the complexity and variety of organic molecules. As a result, only a handful of relatively simple organic molecules, requiring a small number of synthetic steps, have been made in an automated fashion. Here we report an automated assembly-line synthesis that allows iterative formation of C(sp3)–C(sp3) bonds with high stereochemical control and reproducibility, enabling access to complex organic molecules. This was achieved on a commercially available robotic platform capable of handling air-sensitive reactants and performing low-temperature reactions, which enabled six sequenced one-carbon homologations of organoboron substrates to be performed iteratively without human intervention. Together with other automated functional group manipulations, this methodology has been exploited to rapidly build the core fragment of the natural product (+)-kalkitoxin, thus expanding the field of automated organic synthesis.
For details:
Automated Stereocontrolled Assembly-Line Synthesis of Organic Molecules
Valerio Fasano, Rory C. Mykura, James M. Fordham, Jack J. Rogers, Borys Banecki, Adam Noble & Varinder K. Aggarwal
School of Chemistry, University of Bristol, Cantock’s Close, Bristol, BS8 1TS, U.K
Nature Synthesis
https://doi.org/10.1038/s44160-022-00158-6
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