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

摘要

In this account we describe the evolution of our successful efforts to develop a modular synthesis of teraryl-based a-helix mimetics as potential inhibitors of protein-protein interactions. At the center of our convergent synthetic route are 2-substituted 4-io-dophenyl 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 a-helix mimetics using a set of 2 × 18 building blocks featuring the side chains of the 18 proteinogenic amino acids that are of relevance for protein-protein interactions.