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Enantioselective sulfonylation reactions mediated by a tetrapeptide catalyst

Nature Chemistry volume 1, pages 630–634 (2009)Cite this article

Abstract

Nature excels at performing selective modifications of complex polyfunctional molecules by tailoring enzymes, but synthetic chemistry has lagged behind in this regard. In prior work, we have applied a biomimetic approach to this problem, developing small peptides to achieve various group transfer reactions on polyol substrates with high enantio- or regioselectivity. The use of sulfonates as synthetic building blocks and the scarcity of direct, selective methods for their preparation prompted our investigation into this area. In this article we report the development of a π-methyl histidine-based tetrameric peptide that effects the desymmetrization of meso-1,3-diols through enantioselective mono(sulfonylation). The catalyst exhibits structural similarities to another catalyst found to be effective in orthogonal group transfers, but results in modification of the enantiotopic alcohol. The practical and mechanistic implications of this discovery may extend beyond synthetic considerations and provide analogies to the diverse roles of histidine in enzyme active sites.

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Figure 1: π-Methyl-histidine-containing peptides for group transfer chemistry.
Figure 2: The influence of the arene-sulfonyl chloride on the enantioselectivity and yield.
Figure 3: Kinetic resolution of racemic mono(sulfonate) 2a.
Figure 4: Chirality of proline determines the absolute sense of asymmetric induction.
Figure 5: Determination of absolute configuration of sulfonates by comparison to phosphorylation.

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Acknowledgements

This work is supported by the National Institutes of Health (NIH) (GM-068649). K.W.F. would like to thank the NIH for a postdoctoral fellowship (1F32GM083622).

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Authors and Affiliations

  1. Department of Chemistry, Yale University, PO Box 208107, New Haven, 06520-8107, Connecticut, USA

    Kristin Williams Fiori, Angela L. A. Puchlopek & Scott J. Miller

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  1. Kristin Williams Fiori
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  3. Scott J. Miller
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Contributions

All authors conceived and designed the experiments and analysed the data. K.W.F and A.L.A.P. performed the experiments, K.W.F and S.J.M. wrote the paper jointly, and all authors edited and commented on the manuscript.

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Correspondence to Scott J. Miller.

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Fiori, K., Puchlopek, A. & Miller, S. Enantioselective sulfonylation reactions mediated by a tetrapeptide catalyst. Nature Chem 1, 630–634 (2009). https://doi.org/10.1038/nchem.410

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