One of the most important reactions in organic chemistry—amide bond formation—is often overlooked as a contemporary challenge because of the widespread occurrence of amides in modern pharmaceuticals and biologically active compounds. But existing methods are reaching their inherent limits, and concerns about their waste and expense are becoming sharper. Novel chemical approaches to amide formation are therefore being developed. Here we review and summarize a new generation of amide-forming reactions that may contribute to solving these problems. We also consider their potential application to current synthetic challenges, including the development of catalytic amide formation, the synthesis of therapeutic peptides and the preparation of modified peptides and proteins.
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J.W.B. is grateful for the support of diverse agencies for the development of new methods for amide formation, including the Arnold and Mabel Beckman Foundation, the David and Lucille Packard Foundation, Research Corporation for Science Advancement, the US National Institutes of Health (NIH-NIGMS) and the Swiss National Science Foundation (200021-131957). V.R.P. is supported by an ETH Fellowship. We thank all our past and present co-workers who have contributed to the discovery and development of new amide-forming reactions.
The authors declare no competing financial interests.
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Pattabiraman, V., Bode, J. Rethinking amide bond synthesis. Nature 480, 471–479 (2011). https://doi.org/10.1038/nature10702
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