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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
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 a benzene core unit featuring two halide leaving groups of different...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304293/ https://www.ncbi.nlm.nih.gov/pubmed/35910460 http://dx.doi.org/10.1002/ejoc.202101279 |
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author | Trobe, Melanie Blesl, Julia Vareka, Martin Schreiner, Till Breinbauer, Rolf |
author_facet | Trobe, Melanie Blesl, Julia Vareka, Martin Schreiner, Till Breinbauer, Rolf |
author_sort | Trobe, Melanie |
collection | PubMed |
description | 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 a benzene core unit featuring two halide leaving groups of differentiated reactivity in the Pd‐catalyzed cross‐coupling used for teraryl assembly. The use of para‐bromo iodoarene core fragments resolved the issue of hydrolysis during cross‐coupling that was observed when using triflate as a leaving group. We report a complete set of para‐bromoiodoarene core fragments 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 and Val). In order to be compatible with general cross‐coupling conditions, some of the nucleophilic side chains had to be provided in a protected form to serve as stable building blocks. |
format | Online Article Text |
id | pubmed-9304293 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93042932022-07-28 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 Trobe, Melanie Blesl, Julia Vareka, Martin Schreiner, Till Breinbauer, Rolf European J Org Chem Research Articles 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 a benzene core unit featuring two halide leaving groups of differentiated reactivity in the Pd‐catalyzed cross‐coupling used for teraryl assembly. The use of para‐bromo iodoarene core fragments resolved the issue of hydrolysis during cross‐coupling that was observed when using triflate as a leaving group. We report a complete set of para‐bromoiodoarene core fragments 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 and Val). In order to be compatible with general cross‐coupling conditions, some of the nucleophilic side chains had to be provided in a protected form to serve as stable building blocks. John Wiley and Sons Inc. 2022-02-24 2022-05-06 /pmc/articles/PMC9304293/ /pubmed/35910460 http://dx.doi.org/10.1002/ejoc.202101279 Text en © 2022 The Authors. European Journal of Organic Chemistry published by Wiley-VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Trobe, Melanie Blesl, Julia Vareka, Martin Schreiner, Till Breinbauer, Rolf 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 |
title | 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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | modular synthesis of teraryl‐based α‐helix mimetics, part 4: core fragments with two halide leaving groups featuring side chains of proteinogenic amino acids |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304293/ https://www.ncbi.nlm.nih.gov/pubmed/35910460 http://dx.doi.org/10.1002/ejoc.202101279 |
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