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Making carbon-nitrogen bonds in biological and chemical synthesis

Nature Chemical Biology volume 2, pages 284–287 (2006)Cite this article

The function of many biologically active molecules requires the presence of carbon-nitrogen bonds in strategic positions. The biosynthetic pathways leading to such bonds can be bypassed through chemical synthesis to synthesize natural products more efficiently and also to generate the molecular diversity unavailable in nature.

The enormous molecular diversity of natural products is achieved through elaborate biosynthetic pathways, and secondary metabolites are a particularly fascinating and rich source of biological activity. Natural products have undergone extensive optimization throughout evolution. The structures of natural products have been well tuned to allow optimal interaction with biomolecular targets, a characteristic that makes them blueprints for drug discovery. In fact, close to 50% of all drugs originate from natural products1. Not surprisingly, higher hit rates are typically seen in the biological screening of libraries containing natural product–like molecules than in the screening of libraries of purely synthetic molecules2. The privileged skeletons3 of steroids, alkaloids and polypropionates are present in molecules that are recognized by their biological targets with high specificity. Lately, improving the skeletal diversity of synthetic compound collections has been an important goal of synthesis4. The balance of heteroatom substituents in a molecule is crucial to both its biological activity and its potential as a drug5. In this commentary, we trace the origin of some of the key heteroatoms that are present in biologically active molecules and explore the ways in which biological and chemical syntheses differ in their approaches to carbon-nitrogen bond formation.

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Figure 1: Nitrogen-containing fragments are key to biological activity.
Figure 2
Figure 3: Oxygen transfer: monooxygenase versus synthetic catalysts.

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  1. the Department of Chemistry, Davenport Research Laboratories, University of Toronto, 80 St. George Street, Toronto, M5S 3H6, Ontario, Canada

    Ryan Hili & Andrei K Yudin

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  1. Ryan Hili
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  2. Andrei K Yudin
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Hili, R., Yudin, A. Making carbon-nitrogen bonds in biological and chemical synthesis. Nat Chem Biol 2, 284–287 (2006). https://doi.org/10.1038/nchembio0606-284

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