Synthesis and Biological Evaluation of Gramicidin S-Inspired Cyclic Mixed α/β-Peptides

Authors

  • Matthijs van der Knaap,

    1. Bio-Organic Synthesis, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands (fax: +31-71-5274307)
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  • Fatih Basalan,

    1. Bio-Organic Synthesis, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands (fax: +31-71-5274307)
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  • Henny C. van de Mei,

    1. UMCG: Biomaterials, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands
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  • Henk J. Busscher,

    1. UMCG: Biomaterials, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands
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  • Gijsbert A. van der Marel,

    1. Bio-Organic Synthesis, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands (fax: +31-71-5274307)
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  • Herman S. Overkleeft,

    1. Bio-Organic Synthesis, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands (fax: +31-71-5274307)
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  • Mark Overhand

    Corresponding author
    1. Bio-Organic Synthesis, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands (fax: +31-71-5274307)
    • Bio-Organic Synthesis, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands (fax: +31-71-5274307)
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Abstract

Via a Mannich reaction involving a dibenzyliminium species and the titanium enolates of Evans' chiral acylated oxazolidinones the β2-amino acids (R)- and (S)-Fmoc-β2homovaline and (R)-Fmoc-β2homoleucine are synthesized. These building blocks were used, in combination with commercially available α- and β3-amino acids, for the synthesis of the cyclo-(αβ3αβ2α)2 peptide 2 and the cyclo-(αβ2αβ3α)2 peptides 35. The peptides 25 were screened for their ability to inhibit a small panel of Gram-negative and Gram-positive bacterial strains.

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