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The total synthesis of hyperpapuanone, hyperibone L, epi-clusianone and oblongifolin A

Nature Chemistry volume 3, pages 938–942 (2011)Cite this article

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Abstract

Polyprenylated polycyclic acylphloroglucines (PPAPs) are a family of natural products that possess a wide range of different important biological activities because of the relative position and configuration of four substituents that decorate one common central bicyclo[3.3.1]nonane-2,4,9-trione core. The rigid bicyclic framework with its lipophilic side chains and its hydrophilic trione moiety represents a nature-derived lead structure that arranges the substituents (R1 to R4) into a defined topographical orientation. As the substituents are responsible for the biological activities, the seven-step synthetic approach presented here sets the stage for an iterative introduction of R1 to R4 and thus generates structurally diverse trans-type B PPAPs. Four natural and one non-natural trans-type B PPAPs were prepared starting from acetylacetone with overall yields that ranged from 6 to 22%. The concept of separating framework construction from decorating transformations plus the minimization of protecting-group operations are the key issues for the realization of our synthetic approach.

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Figure 1: Classification of PPAPs and total syntheses accomplished.
Figure 2: Retrosynthetic analysis.
Figure 3: Total synthesis of oblongifolin A (1), hyperpapuanone (4), epi-clusianone (2), hyperibone L (3) and regio-hyperpapuanone (5).
Figure 4: Stereochemical rationale for the allylations and Dieckmann condensation.
Figure 5: Structural confirmation of hyperpapuanone (4).

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Acknowledgements

Dedicated to Barry M. Trost on the occasion of his 70th birthday. The authors thank the Deutsche Forschungsgemeinschaft, the Deutsche Krebshilfe e.V., the Landesgraduiertenstiftung Baden-Württemberg (PhD grant for N.B.) and the Studienstiftung des deutschen Volkes (PhD grant for K.M.) for financial support.

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  1. Institut für Organische Chemie, Universität Stuttgart, Pfaffenwaldring 55, Stuttgart, D-70569, Germany

    Nicole Biber, Katrin Möws & Bernd Plietker

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  2. Katrin Möws
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Contributions

N.B. prepared the natural products 1 – 5 . K.M. was involved in model studies towards the synthesis of O-methyl hyperibone and crystallized this compound (see Supplementary Information). B.P. designed the study, analysed the data and wrote the paper. All the authors discussed the results and commented on the manuscript.

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Correspondence to Bernd Plietker.

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Crystallographic data for compound 21 (CIF 23 kb)

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Biber, N., Möws, K. & Plietker, B. The total synthesis of hyperpapuanone, hyperibone L, epi-clusianone and oblongifolin A. Nature Chem 3, 938–942 (2011). https://doi.org/10.1038/nchem.1170

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