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An efficient synthesis of loline alkaloids

Nature Chemistry volume 3, pages 543–545 (2011)Cite this article

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Abstract

Loline (1) is a small alkaloid that, in spite of its simple-looking structure, has posed surprising challenges to synthetic chemists. It has been known for more than a century and has been the subject of extensive biological investigations, but only two total syntheses have been achieved to date. Here, we report an asymmetric total synthesis of loline that, with less then ten steps, is remarkably short. Our synthesis incorporates a Sharpless epoxidation, a Grubbs olefin metathesis and an unprecedented transannular aminobromination, which converts an eight-membered cyclic carbamate into a bromopyrrolizidine. The synthesis is marked by a high degree of chemo- and stereoselectivity and gives access to several members of the loline alkaloid family. It delivers sufficient material to support a programme aimed at studying the complex interactions between plants, fungi, insects and bacteria brokered by loline alkaloids.

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Figure 1: Loline alkaloids.
Figure 2: Short total synthesis of loline alkaloids.
Figure 3: Mechanism of the key step.
Figure 4: Synthesis and X-ray structure of temuline carbamate.

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Acknowledgements

The authors thank undergraduate participants E. Zeynep Serdar and C. Hieke, and thank E. Lauterwasser, E. Downs-Beaulieu and C.A. Kuttruff for insightful discussions.

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Authors and Affiliations

  1. Department of Chemistry and Pharmacology, Ludwig-Maximilians-Universität, München, and Center for Integrated Protein Science, Munich, 81377, Germany

    Mesut Cakmak, Peter Mayer & Dirk Trauner

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  1. Mesut Cakmak
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  2. Peter Mayer
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  3. Dirk Trauner
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Contributions

M.C. and D.T. conceived the synthetic route and wrote the manuscript. M.C. conducted the experimental work, analysed the results and wrote the Supplementary Information. P.M. solved the crystal structures.

Corresponding author

Correspondence to Dirk Trauner.

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The authors declare no competing financial interests.

Supplementary information

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Supplementary information (PDF 1996 kb)

Supplementary information

Crystallographic data for compound 14 (CIF 15 kb)

Supplementary information

Crystallographic data for compound 20 (CIF 19 kb)

Supplementary information

Crystallographic data for compound 22 (CIF 15 kb)

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Cakmak, M., Mayer, P. & Trauner, D. An efficient synthesis of loline alkaloids. Nature Chem 3, 543–545 (2011). https://doi.org/10.1038/nchem.1072

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