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A Modular Synthesis of Teraryl-Based α-Helix Mimetics, Part 1: Synthesis of Core Fragments with Two Electronically Differentiated Leaving Groups

Authors

  • Dr. Martin Peters,

    1. Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 9, 8010 Graz (Austria), Fax: (+43) 316-873-32402
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    • These authors contributed equally to this work.

  • Melanie Trobe,

    1. Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 9, 8010 Graz (Austria), Fax: (+43) 316-873-32402
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    • These authors contributed equally to this work.

  • Dipl.-Chem. Hao Tan,

    1. Max-Planck-Institute for Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund (Germany) and Technische Universität Dortmund, Organische Chemie, Otto-Hahn-Str. 6, 44227 Dortmund (Germany)
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  • Dr. Rolf Kleineweischede,

    1. Max-Planck-Institute for Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund (Germany) and Technische Universität Dortmund, Organische Chemie, Otto-Hahn-Str. 6, 44227 Dortmund (Germany)
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  • Prof. Dr. Rolf Breinbauer

    Corresponding author
    1. Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 9, 8010 Graz (Austria), Fax: (+43) 316-873-32402
    2. Max-Planck-Institute for Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund (Germany) and Technische Universität Dortmund, Organische Chemie, Otto-Hahn-Str. 6, 44227 Dortmund (Germany)
    • Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 9, 8010 Graz (Austria), Fax: (+43) 316-873-32402
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Abstract

Teraryl-based α-helix mimetics have proven to be useful compounds for the inhibition of protein–protein interactions (PPI). We have developed a modular and flexible approach for the synthesis of teraryl-based α-helix mimetics. Central to our strategy is the use of a benzene core unit featuring two leaving groups of differentiated reactivity in the Pd-catalyzed cross-coupling used for terphenyl assembly. With the halogen/diazonium route and the halogen/triflate route, two strategies have successfully been established. The synthesis of core building blocks with aliphatic (Ala, Val, Leu, Ile), aromatic (Phe), polar (Cys, Lys), hydrophilic (Ser, Gln), and acidic (Glu) amino acid side chains are reported.

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