title: 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.
abstract: One of the most common protein-protein interactions (PPI) is the interaction of the α-helix of one protein with the surface of the second one. Terphenylic scaffolds are bioinspired motifs in the inhibition of PPIs and have been identified as suitable α-helix mimetics. One of the challenging aspects of this strategy is the poor solubility of terphenyls under physiological conditions. In the literature pyrrolopyrimidine-, pyrimidine- or pyridazine-based mimetics have been reported to show improved solubility. We present a new convergent strategy for the synthesis of linear pyridine-type teraryls based on a phenylic core unit. A general approach for the synthesis of 3,5-disubstituted pyridine-based boronic acid pinacol esters with amino acid side chains in the 3-position (representing Phe, Leu, Ile, Lys, Asp, Asn) is presented and exploits the functional group tolerance of the Knochel-Grignard reagents. The building blocks have been used in a convergent in situ two-step synthesis of teraryl α-helix mimetics.
authors.affiliation: Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 9, 8010 Graz, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Peters
authors.forename: Melanie
authors.initials: M
authors.lastname: Trobe
authors.forename: Rolf
authors.initials: R
authors.lastname: Breinbauer
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D001897:Boronic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011724:Pyridazines / Q000737:chemistry*; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: C583003:5-pyridine boronic acid pinacol ester; D000596:Amino Acids; D001897:Boronic Acids; D011724:Pyridazines; D011725:Pyridines; C062482:pyridazine