Modular Synthesis of Teraryl-based alpha-Helix Mimetics, Part 4: Core Fragments with two Halide Leaving Groups Featuring Side Chains of Proteinogenic Amino Acids

Melanie Trobe, Julia Blesl, Martin Vareka, Till Schreiner, Rolf Breinbauer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 using a benzene core unit featuring two halide leaving groups of differentiated reactivity in the Pd-catalyzed cross-coupling used for teraryl assembly. The use of para-bromo iodoarene core fragments resolved the issue of hydrolysis during cross-coupling that was observed when using triflate as a leaving group. We report a complete set of para-bromoiodoarene core fragments decorated with side chains of all proteinogenic amino acids relevant for PPI (Ala, Arg, Asn, Asp, Cys, Gln, Glu, His, Ile, Leu, Lys, Met, Phe, Ser, Thr, Trp, Tyr and Val). In order to be compatible with general cross-coupling conditions, some of the nucleophilic side chains had to be provided in a protected form to serve as stable building blocks.

Original languageEnglish
Article numbere202101279
Number of pages8
JournalEuropean Journal of Organic Chemistry
Volume2022
Issue number17
Early online date2022
DOIs
Publication statusPublished - 6 May 2022

Keywords

  • Imidazole
  • Inhibitors
  • Peptide mimetics
  • Protein-protein interaction
  • Suzuki coupling

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry

Fields of Expertise

  • Human- & Biotechnology

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