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Terpene cyclization catalysed inside a self-assembled cavity

Abstract

In nature, complex terpene natural products are formed by the so-called tail-to-head terpene (THT) cyclization. The cationic reaction cascade is promoted efficiently in complex enzyme pockets, in which cationic intermediates and transition states are stabilized. In solution, the reaction is hard to control and man-made catalysts able to perform selective THT cyclizations are lacking. We herein report the first example of a successful THT cyclization inside a supramolecular structure. The basic mode of operation in cyclase enzymes was mimicked successfully and a catalytic non-stop THT was achieved with geranyl acetate as the substrate. The results presented have implications for the postulated reaction mechanism in cyclase enzymes. Evidence indicates that the direct isomerization of a geranyl cation to the cisoid isomer, which so far was considered unlikely, is feasible.

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Figure 1: Biosynthesis of cyclic terpene natural products.
Figure 2: Structure of the resorcinarene capsule I.
Figure 3: Results of the THT cyclizations with catalyst I for the alcohol substrates.
Figure 4: Results of the THT cyclizations with catalyst I for the acetate substrates.

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Acknowledgements

This project was supported by the Bayerischen Akademie der Wissenschaften (Junges Kolleg), Fonds der Chemischen Industrie (Sachkostenzuschuss), the TUM Junior Fellow Fund and the Dr.-Ing. Leonhard-Lorenz-Stiftung. The help of J. Richers with the graphical design is gratefully acknowledged.

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K.T. conceived the project and wrote the manuscript with Q.Z. Q.Z. planned and carried out the experiments. K.T. and Q.Z. discussed the experiments and results.

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Correspondence to K. Tiefenbacher.

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The authors declare no competing financial interests.

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Zhang, Q., Tiefenbacher, K. Terpene cyclization catalysed inside a self-assembled cavity. Nature Chem 7, 197–202 (2015). https://doi.org/10.1038/nchem.2181

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