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A Modular Synthesis of Teraryl‐Based α‐Helix Mimetics, Part 5: A Complete Set of Pyridine Boronic Acid Pinacol Esters Featuring Side Chains of Proteinogenic Amino Acids

ABSTRACT: 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 pyridine containing boronic acid building blocks to increase the water solubility. Following our initial publication in which we have introduced the methodology in combination with sequential Pd‐catalyzed cross‐coupling for teraryl assembly, we can now report a complete set of pyridine based boronic acid building blocks 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, Val) to complement the core fragment set. For a representative set of teraryls we have studied the influence of the pyridine rings on the solubility of the assembled oligoarenes. A set of 5‐substituted 3‐pyridine boronic acid pinacol esters decorated with the side chains of all proteinogenic amino acids relevant in protein‐protein interactions is reported. This work completes our efforts towards a library of building blocks for the modular assembly of teraryl‐based α‐helix mimetics via sequential Pd cross‐coupling.

SUBMITTER: Trobe M

PROVIDER: S-EPMC9304165 | biostudies-literature |

REPOSITORIES: biostudies-literature

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