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. Issue 7 (23rd December 2012)

• Record Type: Journal Article
• Authors: Peters, Martin; Trobe, Melanie; Breinbauer, Rolf
• Is Part Of: Chemistry. Volume 19:Issue 7(2013)
• Page Start: 2450
• Page End: 2456
• Publication Date: 2012-12-23
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201203006
• Languages: English
• ISSNs: 0947-6539

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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.</p> </abstract>