Stereochemical assignment of the protein-protein interaction inhibitor JBIR-22 by total synthesis

Alan Healy; Miho Izumikawa; Alexandra Martha Zoya Slawin; Kazuo Shin-ya; Nicholas James Westwood

doi:10.1002/anie.201411141

Stereochemical assignment of the protein-protein interaction inhibitor JBIR-22 by total synthesis

Alan Healy, Miho Izumikawa, Alexandra Martha Zoya Slawin, Kazuo Shin-ya, Nicholas James Westwood

Research output: Contribution to journal › Article › peer-review

Abstract

Recent reports have highlighted the biological activity associated with a sub-family of the tetramic acid class of natural products. Despite the fact that members of this sub-family act as protein-protein interaction inhibitors of relevance to proteasome assembly, no synthetic work has been reported. This may be because this sub-family contains an unnatural 4,4-disubstitued glutamic acid, the synthesis of which provides a key challenge. Here we describe a highly stereoselective route to a masked form of this unnatural amino acid. This enabled the synthesis of two of the possible diastereomers of JBIR-22 and allowed its relative and absolute stereochemistry to be assigned.

Original language	English
Pages (from-to)	4046-4050
Journal	Angewandte Chemie
Volume	54
Issue number	13
Early online date	4 Feb 2015
DOIs	https://doi.org/10.1002/anie.201411141
Publication status	Published - 23 Mar 2015

Keywords

Natural products
Stereochemistry
Tetramic acids
Total synthesis
Unnatural amino acids

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10.1002/anie.201411141

healy2015angewandtechemiint4046
Copyright 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. 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.
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Structuring the Future: Structuring the Future - Underpinning world-leading science in EaStCHEM through cutting edge characterisation
Woollins, J. D. (PI), Ashbrook, S. E. (CoI), Morris, R. E. (CoI) & Slawin, A. M. Z. (CoI)
EPSRC
1/01/13 → 31/03/13
Project: Standard

The Cambridge Crystallographic Data Centre - deposition number 1034467
Healy, A. (Creator), Izumikawa, M. (Creator), Slawin, A. M. Z. (Creator), Shin-ya, K. (Creator) & Westwood, N. J. (Creator), Cambridge Crystallographic Data Centre, 2015
https://dx.doi.org/10.5517/cc13qfx5
Dataset

Cite this

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title = "Stereochemical assignment of the protein-protein interaction inhibitor JBIR-22 by total synthesis",

abstract = "Recent reports have highlighted the biological activity associated with a sub-family of the tetramic acid class of natural products. Despite the fact that members of this sub-family act as protein-protein interaction inhibitors of relevance to proteasome assembly, no synthetic work has been reported. This may be because this sub-family contains an unnatural 4,4-disubstitued glutamic acid, the synthesis of which provides a key challenge. Here we describe a highly stereoselective route to a masked form of this unnatural amino acid. This enabled the synthesis of two of the possible diastereomers of JBIR-22 and allowed its relative and absolute stereochemistry to be assigned.",

keywords = "Natural products, Stereochemistry, Tetramic acids, Total synthesis, Unnatural amino acids",

author = "Alan Healy and Miho Izumikawa and Slawin, {Alexandra Martha Zoya} and Kazuo Shin-ya and Westwood, {Nicholas James}",

note = "The authors acknowledge the EPSRC and Cancer Research UK (CRUK Grant No. C21383/A6950) for funding this research. ",

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doi = "10.1002/anie.201411141",

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AU - Healy, Alan

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AU - Shin-ya, Kazuo

AU - Westwood, Nicholas James

N1 - The authors acknowledge the EPSRC and Cancer Research UK (CRUK Grant No. C21383/A6950) for funding this research.

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KW - Stereochemistry

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KW - Total synthesis

KW - Unnatural amino acids

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DO - 10.1002/anie.201411141

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JO - Angewandte Chemie

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Stereochemical assignment of the protein-protein interaction inhibitor JBIR-22 by total synthesis

Abstract

Keywords

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Projects

Structuring the Future: Structuring the Future - Underpinning world-leading science in EaStCHEM through cutting edge characterisation

Datasets

The Cambridge Crystallographic Data Centre - deposition number 1034467

Cite this