Abstract
Natural product synthesis remains one of the most vibrant and intellectually rewarding areas of chemistry, although the justifications for pursuing it have evolved over time. In the early years, the emphasis lay on structure elucidation and confirmation through synthesis, as exemplified by celebrated studies on cocaine, morphine, strychnine and chlorophyll. This was followed by a phase where the sheer demonstration that highly complex molecules could be recreated in the laboratory in a rational manner was enough to justify the economic expense and intellectual agonies of a synthesis. Since then, syntheses of natural products have served as platforms for the demonstration of elegant strategies, for inventing new methodology ‘on the fly’ or to demonstrate the usefulness and scope of methods established with simpler molecules. We now add another aspect that we find fascinating, viz. ‘natural product anticipation’. In this Review, we survey cases where the synthesis of a compound in the laboratory has preceded its isolation from nature. The focus of our Review lies on examples where this anticipation of a natural product has triggered a successful search or where synthesis and isolation have occurred independently. Finally, we highlight cases where a potential natural product structure has been suggested as a result of synthetic endeavours but not yet confirmed by isolation, inviting further collaborations between synthetic and natural product chemists.
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Change history
22 February 2022
A Correction to this paper has been published: https://doi.org/10.1038/s41570-022-00374-w
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Acknowledgements
B.E.H. thanks New York University for a MacCracken fellowship. The authors thank B. S. Matsuura for helpful discussions. The authors thank B. S. Matsuura, A. J. E. Novak and K.-P. Rühmann for their critical review of the manuscript.
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Hetzler, B.E., Trauner, D. & Lawrence, A.L. Natural product anticipation through synthesis. Nat Rev Chem 6, 170–181 (2022). https://doi.org/10.1038/s41570-021-00345-7
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