The Development of a Modular Synthesis of Teraryl-Based α-Helix Mimetics as Potential Inhibitors of Protein-Protein Interactions

In this account we describe the evolution of our successful efforts to develop a modular synthesis of teraryl-based -helix mimetics as potential inhibitors of protein-protein interactions. At the center of our convergent synthetic route are 2-substituted 4-iodophenyl triflates as core fragments, which by consecutive Suzuki couplings with 5-substituted pyridin-3-ylboronic acids are converted into the desired teraryl compounds. With our strategy it should be possible to synthesize all 5670 variants of the teraryl -helix mimetics using a set of 2 x 18 building blocks featuring the side chains of the 18 proteinogenic amino acids that are of relevance for protein-protein interactions. 1Introduction and Concept 1.1Protein-Protein Interactions 1.2-Helix Mimetics 1.3Linear Synthesis of -Helix Mimetics 2Modular Synthetic Route to Teraryls 2.1Core Fragments 2.2Pyridinylboronic Acids 3Conclusion and Outlook