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Natural products as inspiration for the development of asymmetric catalysis

Nature volume 455, pages 323–332 (2008)Cite this article

Abstract

Biologically active natural products often contain particularly challenging structural features and functionalities in terms of synthesis. Perhaps the greatest difficulties are those caused by issues of stereochemistry. A useful strategy for synthesizing such molecules is to devise methods of bond formation that provide opportunities for using enantioselective catalysis. In using this tactic, the desire for a particular target structure ultimately drives the development of catalytic methods. New enantioselective catalytic methods contribute to a greater fundamental understanding of how bonds can be constructed and lead to valuable synthetic technologies that are useful for a variety of applications.

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Figure 1: Selected examples of enantioselective catalysis in total synthesis.
Figure 2: Asymmetric hydrogenation of β-enamino amides towards Januvia.
Figure 3: Enantioselective C(sp3)−C(sp3) cross-coupling towards fluvirucinine A1.
Figure 4: Asymmetric Heck cyclization towards minfiensine.
Figure 5: Amine-catalysed indole alkylation towards flustramine B.
Figure 6: Enantioselective Pictet–Spengler cyclization towards harmicine.
Figure 7: Asymmetric phase-transfer alkylation towards indacrinone.
Figure 8: Double enantioselective enolate alkylation and the synthesis of cyanthiwigin F.
Figure 9: Enantioselective TMM [3 + 2] cyclization towards marcfortine B.

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Acknowledgements

We thank the National Institute of General Medical Sciences (grant number R01GM080269-01), Eli Lilly (which provided predoctoral fellowships to J.T.M. and M.R.K.), Amgen, Abbott Laboratories, Boehringer Ingelheim, Merck, Bristol–Myers Squibb and the California Institute of Technology for financial support.

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    Justin T. Mohr, Michael R. Krout & Brian M. Stoltz

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Mohr, J., Krout, M. & Stoltz, B. Natural products as inspiration for the development of asymmetric catalysis. Nature 455, 323–332 (2008). https://doi.org/10.1038/nature07370

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