PDF icon Download PDF
Synlett 2014; 25(09): 1202-1214
DOI: 10.1055/s-0033-1340740
account
© Georg Thieme Verlag Stuttgart · New York

The Development of a Modular Synthesis of Teraryl-Based α-Helix Mimetics as Potential Inhibitors of Protein–Protein Interactions

Melanie Trobe
a   Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 9, 8010 Graz, Austria   Fax: +43(316)87332402   Email: breinbauer@tugraz.at
,
Martin Peters
a   Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 9, 8010 Graz, Austria   Fax: +43(316)87332402   Email: breinbauer@tugraz.at
b   Fraunhofer Project Group Electrochemical Energy Storage, Fraunhofer Institute of Chemical Technology ICT, Parkring 6, 85748 Garching b. München, Germany
,
Sebastian H. Grimm
a   Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 9, 8010 Graz, Austria   Fax: +43(316)87332402   Email: breinbauer@tugraz.at
,
Rolf Breinbauer*
a   Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 9, 8010 Graz, Austria   Fax: +43(316)87332402   Email: breinbauer@tugraz.at
› Author Affiliations
Further Information

Publication History

Received: 24 November 2013

Accepted after revision: 08 January 2014

Publication Date:
02 April 2014 (online)

   Permissions and Reprints All articles of this category


Preview

Dedicated to Professor Manfred T. Reetz on the occasion of his 70th birthday.

Abstract

In this account we describe the evolution of our successful efforts to develop a modular synthesis of teraryl-based α-helix mimetics as potential inhibitors of protein–protein interactions. At the center of our convergent synthetic route are 2-substituted 4-iodophenyl triflates as core fragments, which by consecutive Suzuki couplings with 5-substituted pyridin-3-ylboronic acids are converted into the desired teraryl compounds. With our strategy it should be possible to synthesize all 5670 variants of the teraryl α-helix mimetics using a set of 2 × 18 building blocks featuring the side chains of the 18 proteinogenic amino acids that are of relevance for protein–protein interactions.

1 Introduction and Concept

1.1 Protein–Protein Interactions

1.2 α-Helix Mimetics

1.3 Linear Synthesis of α-Helix Mimetics

2 Modular Synthetic Route to Teraryls

2.1 Core Fragments

2.2 Pyridinylboronic Acids

3 Conclusion and Outlook

Key words

cross-coupling - Grignard reactions - inhibitors - peptides - pyridines