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Synthesis of macrolactam analogues of radicicol and their binding to heat shock protein Hsp90

Dutton, Bridie L.; Kitson, Russell R.A.; Parry-Morris, Sarah; Roe, S. Mark; Prodromou, Chrisostomos; Moody, Christopher J.

Synthesis of macrolactam analogues of radicicol and their binding to heat shock protein Hsp90 Thumbnail


Authors

Bridie L. Dutton

Russell R.A. Kitson

Sarah Parry-Morris

S. Mark Roe

Chrisostomos Prodromou

Christopher J. Moody



Abstract

A series of macrolactam analogues of the naturally occurring resorcylic acid lactone radicicol have been synthesised from methyl orsellinate in 7 steps, involving chlorination, protection of the two phenolic groups, and hydrolysis to the benzoic acid. Formation of the dianion and quenching with a Weinreb amide results in acylation of the toluene methyl group that is followed by amide formation and ring closing metathesis to form the macrocyclic lactam. Final deprotection of the phenolic groups gives the desired macrolactams whose binding to the N-terminal domain of yeast Hsp90 was studied by isothermal titration calorimetry and protein X-ray crystallography.

Citation

Dutton, B. L., Kitson, R. R., Parry-Morris, S., Roe, S. M., Prodromou, C., & Moody, C. J. (2014). Synthesis of macrolactam analogues of radicicol and their binding to heat shock protein Hsp90. Organic and Biomolecular Chemistry, 12(8), https://doi.org/10.1039/C3OB42211A

Journal Article Type Article
Acceptance Date Jan 9, 2014
Online Publication Date Jan 10, 2014
Publication Date Feb 28, 2014
Deposit Date Jul 30, 2014
Publicly Available Date Jul 30, 2014
Journal Organic and Biomolecular Chemistry
Print ISSN 1477-0520
Electronic ISSN 1477-0520
Publisher Royal Society of Chemistry
Peer Reviewed Peer Reviewed
Volume 12
Issue 8
DOI https://doi.org/10.1039/C3OB42211A
Public URL https://nottingham-repository.worktribe.com/output/722644
Publisher URL http://pubs.rsc.org/en/Content/ArticleLanding/2014/OB/c3ob42211a#!divAbstract

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