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Improved and scalable synthesis of building blocks for the modular synthesis of teraryl-based alpha-helix mimetics

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Abstract

The modular synthesis of teraryl-based alpha-helix mimetics can be accomplished by sequential Suzuki-couplings of arylboronic acid building blocks with 4-iodophenyltriflate core-fragments. We report about new synthetic accesses to core fragments featuring the side chains of Leu, Lys, Cys, Glu, Gln, Ser, and Thr starting from simple phenol precursors.

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Acknowledgments

We thank Michael Bumberger, Patrick Dobrounig, Anna Schweiger, and Beate Steller for skillful assistance in the lab and Dr. Martin Peters for fruitful discussions in the early phase of this project. This research was funded by grants of the Volkswagenstiftung, Hannover, the PLACEBO (Platform for Chemical Biology) project as part of the Austrian Genome Project GEN-AU funded by the Forschungsförderungsgesellschaft (FFG) and Bundesministerium für Wissenschaft und Forschung (BMWF), and NAWI Graz.

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Correspondence to Rolf Breinbauer.

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Trobe, M., Breinbauer, R. Improved and scalable synthesis of building blocks for the modular synthesis of teraryl-based alpha-helix mimetics. Monatsh Chem 147, 509–521 (2016). https://doi.org/10.1007/s00706-015-1599-0

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Keywords

  • Baeyer–Villiger oxidation
  • Claisen rearrangement
  • Iodination
  • Peptidomimetics
  • Protein–protein interactions
  • Wittig reaction