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Stereochemical Assignment of the Protein–Protein Interaction Inhibitor JBIR-22 by Total Synthesis**

Recent reports have highlighted the biological activity associated with a subfamily of the tetramic acid class of natural products. Despite the fact that members of this subfamily act as protein–protein interaction inhibitors that are of relevance to proteasome assembly, no synthetic work has been r...

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Detalles Bibliográficos
Autores principales: Healy, Alan R, Izumikawa, Miho, Slawin, Alexandra M Z, Shin-ya, Kazuo, Westwood, Nicholas J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: WILEY-VCH Verlag 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4441253/
https://www.ncbi.nlm.nih.gov/pubmed/25650886
http://dx.doi.org/10.1002/anie.201411141
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author Healy, Alan R
Izumikawa, Miho
Slawin, Alexandra M Z
Shin-ya, Kazuo
Westwood, Nicholas J
author_facet Healy, Alan R
Izumikawa, Miho
Slawin, Alexandra M Z
Shin-ya, Kazuo
Westwood, Nicholas J
author_sort Healy, Alan R
collection PubMed
description Recent reports have highlighted the biological activity associated with a subfamily of the tetramic acid class of natural products. Despite the fact that members of this subfamily act as protein–protein interaction inhibitors that are of relevance to proteasome assembly, no synthetic work has been reported. This may be due to the fact that this subfamily contains an unnatural 4,4-disubstitued glutamic acid, the synthesis of which provides a key challenge. A highly stereoselective route to a masked form of this unnatural amino acid now enabled the synthesis of two of the possible diastereomers of JBIR-22 and allowed the assignment of its relative and absolute stereochemistry.
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spelling pubmed-44412532015-05-26 Stereochemical Assignment of the Protein–Protein Interaction Inhibitor JBIR-22 by Total Synthesis** Healy, Alan R Izumikawa, Miho Slawin, Alexandra M Z Shin-ya, Kazuo Westwood, Nicholas J Angew Chem Int Ed Engl Communications Recent reports have highlighted the biological activity associated with a subfamily of the tetramic acid class of natural products. Despite the fact that members of this subfamily act as protein–protein interaction inhibitors that are of relevance to proteasome assembly, no synthetic work has been reported. This may be due to the fact that this subfamily contains an unnatural 4,4-disubstitued glutamic acid, the synthesis of which provides a key challenge. A highly stereoselective route to a masked form of this unnatural amino acid now enabled the synthesis of two of the possible diastereomers of JBIR-22 and allowed the assignment of its relative and absolute stereochemistry. WILEY-VCH Verlag 2015-03-23 2015-02-04 /pmc/articles/PMC4441253/ /pubmed/25650886 http://dx.doi.org/10.1002/anie.201411141 Text en © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. http://creativecommons.org/licenses/by/3.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Communications
Healy, Alan R
Izumikawa, Miho
Slawin, Alexandra M Z
Shin-ya, Kazuo
Westwood, Nicholas J
Stereochemical Assignment of the Protein–Protein Interaction Inhibitor JBIR-22 by Total Synthesis**
title Stereochemical Assignment of the Protein–Protein Interaction Inhibitor JBIR-22 by Total Synthesis**
title_full Stereochemical Assignment of the Protein–Protein Interaction Inhibitor JBIR-22 by Total Synthesis**
title_fullStr Stereochemical Assignment of the Protein–Protein Interaction Inhibitor JBIR-22 by Total Synthesis**
title_full_unstemmed Stereochemical Assignment of the Protein–Protein Interaction Inhibitor JBIR-22 by Total Synthesis**
title_short Stereochemical Assignment of the Protein–Protein Interaction Inhibitor JBIR-22 by Total Synthesis**
title_sort stereochemical assignment of the protein–protein interaction inhibitor jbir-22 by total synthesis**
topic Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4441253/
https://www.ncbi.nlm.nih.gov/pubmed/25650886
http://dx.doi.org/10.1002/anie.201411141
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