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.
Original language | English |
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Pages (from-to) | 2450-2456 |
Journal | Chemistry - a European Journal |
Volume | 19 |
Issue number | 7 |
DOIs | |
Publication status | Published - 2013 |
Fields of Expertise
- Human- & Biotechnology
Treatment code (Nähere Zuordnung)
- Basic - Fundamental (Grundlagenforschung)
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- Experimental