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 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.

• Publication year

  2022

• Venue

  Annalen der Pharmacie

• Publication date

  2022-02-11

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1002/ejoc.202101280PMID 35910461PMCID 9304165
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• 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

  2022cited by this paper
• A Modular Synthesis of Teraryl‐Based α‐Helix Mimetics, Part 3: Iodophenyltriflate Core Fragments Featuring Side Chains of Proteinogenic Amino Acids

  2022cited by this paper
• A Modular Synthesis of Teraryl‐Based α‐Helix Mimetics, Part 4: Core Fragments with Two Halide Leaving Groups Featuring Side Chains of Proteinogenic Amino Acids

  2022cited by this paper
• An α-helix mimetic oligopyridylamide, ADH-31, modulates Aβ42 monomer aggregation and destabilizes protofibril structures: insights from molecular dynamics simulations.

  2020cited by this paper
• A reference map of the human binary protein interactome

  2020cited by this paper
• α-Helix-Mimetic Foldamers for Targeting HIV-1 TAR RNA.

  2019cited by this paper
• Bridged α-helix mimetic small molecules.

  2019cited by this paper
• Pyrrolopyrimidine vs Imidazole-Phenyl-Thiazole Scaffolds in Nonpeptidic Dimerization Inhibitors of Leishmania infantum Trypanothione Reductase.

  2019cited by this paper
• α-Helix Mimetics as Modulators of Aβ Self-Assembly.

  2017cited by this paper
• An α-helical peptidomimetic scaffold for dynamic combinatorial library formation.

  2017cited by this paper
• Architecture of the human interactome defines protein communities and disease networks

  2017cited by this paper
• Small molecules, big targets: drug discovery faces the protein–protein interaction challenge

  2016cited by this paper
• Synthesis of Pyridazine-Based α-Helix Mimetics.

  2016cited by this paper
• MIDA boronates are hydrolysed fast and slow by two different mechanisms

  2016cited by this paper
• Sequential and iterative Pd-catalyzed cross-coupling reactions in organic synthesis

  2016cited by this paper
• A human interactome in three quantitative dimensions organized by stoichiometries and abundances.

  2015cited by this paper
• Stabilizer-Guided Inhibition of Protein-Protein Interactions.

  2015cited by this paper
• Perturbation of the c-Myc-Max protein-protein interaction via synthetic α-helix mimetics.

  2015cited by this paper
• Structure-Based Design of Inhibitors of Protein–Protein Interactions: Mimicking Peptide Binding Epitopes

  2015cited by this paper
• Design, solid-phase synthesis, and evaluation of a phenyl-piperazine-triazine scaffold as α-helix mimetics.

  2014cited by this paper
• Modulators of protein-protein interactions.

  2014cited by this paper
• Stabilization and inhibition of protein-protein interactions: the 14-3-3 case study.

  2013cited by this paper
• Amphipathic α-helix mimetics based on a 1,2-diphenylacetylene scaffold.

  2013cited by this paper
• Highly Functionalized Terpyridines as Competitive Inhibitors of AKAP–PKA Interactions

  2013cited by this paper
• A modular synthesis of teraryl-based α-helix mimetics, part 2: Synthesis of 5-pyridine boronic acid pinacol ester building blocks with amino acid side chains in 3-position.

  2013cited by this paper
• A modular synthesis of teraryl-based α-helix mimetics, part 1: Synthesis of core fragments with two electronically differentiated leaving groups.

  2013cited by this paper
• A General Solution for the 2-Pyridyl Problem

  2012cited by this paper
• Optimizing solubility: kinetic versus thermodynamic solubility temptations and risks.

  2012cited by this paper
• Novel pyrrolopyrimidine-based α-helix mimetics: cell-permeable inhibitors of protein−protein interactions.

  2011cited by this paper
• Synthesis of the phenylpyridal scaffold as a helical peptide mimetic.

  2010cited by this paper
• General method for synthesis of 2-heterocyclic N-methyliminodiacetic acid boronates.

  2010cited by this paper
• A general solution for unstable boronic acids: slow-release cross-coupling from air-stable MIDA boronates.

  2009cited by this paper
• Estimating the size of the human interactome

  2008cited by this paper
• Synthesis and structure of 1,4-dipiperazino benzenes: chiral terphenyl-type peptide helix mimetics.

  2008cited by this paper
• Convenient preparation of polyfunctional aryl magnesium reagents by a direct magnesium insertion in the presence of LiCl.

  2008cited by this paper
• Synthesis of pyridazine-based scaffolds as alpha-helix mimetics.

  2007cited by this paper
• Synthetic non-peptide mimetics of alpha-helices.

  2007cited by this paper
• Regioselective functionalization of trisubstituted pyridines using a bromine-magnesium exchange.

  2006cited by this paper
• Efficient synthesis of functionalized organozinc compounds by the direct insertion of zinc into organic iodides and bromides.

  2006cited by this paper
• Synthesis of a 2,3';6',3''-terpyridine scaffold as an alpha-helix mimetic.

  2005cited by this paper
• Preparation and selective reactions of mixed bimetallic aromatic and heteroaromatic boron-magnesium reagents.

  2005cited by this paper
• A human protein-protein interaction network: a resource for annotating the proteome.

  2005cited by this paper
• Iron-catalyzed cross-coupling reactions.

  2002cited by this paper
• Copper-catalyzed halogen exchange in aryl halides: an aromatic Finkelstein reaction.

  2002cited by this paper
• Toward proteomimetics: terphenyl derivatives as structural and functional mimics of extended regions of an alpha-helix.

  2001cited by this paper
• Protecting Groups for Thiols Suitable for Suzuki Conditions.

  2000cited by this paper

• Enantioselective Total Synthesis of Two Aromatized Halicyclamines.

  2026cites this paper
• Triarylboron-Based Dual Thermally Activated Delayed Fluorescence Emitter for Single Molecule White Light-Emitting Diodes.

  2025cites this paper
• Efficient Chemoselective Sequential Pd-Catalyzed Suzuki Coupling of Highly Functionalized Iodoaryl Triflates

  2025cites this paper
• Successive diastereoselective C(sp3)–H arylation and Suzuki coupling toward enantioenriched polyaryl unnatural amino acid motifs

  2025cites this paper
• Aromatic oligoesters as novel helix mimetic scaffolds

  2023cites this paper
• A Modular Synthesis of Teraryl‐Based α‐Helix Mimetics, Part 4: Core Fragments with Two Halide Leaving Groups Featuring Side Chains of Proteinogenic Amino Acids

  2022cites this paper
• A Modular Synthesis of Teraryl‐Based α‐Helix Mimetics, Part 3: Iodophenyltriflate Core Fragments Featuring Side Chains of Proteinogenic Amino Acids

  2022cites this paper
• 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

  2022cites this paper