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

DOI: 10.1039/c3ob42211a DOI Help
PMID: 24435512 PMID Help

Authors: Bridie Dutton (University of Nottingham) , Russell Kitson (University of Nottingham) , Sarah Parry-morris (University of Sussex) , S. Mark Roe (University of Sussex) , Chrisostomos Prodromou (Institute of Cancer Research) , Christopher J Moody (University of Nottingham)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Organic & Biomolecular Chemistry

State: Published (Approved)
Published: January 2014

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.

Journal Keywords: Crystallography; X-Ray; HSP90; Lactams; Macrocyclic; Macrolides; Models; Molecular; Protein; Saccharomyces; Saccharomyces cerevisiae Proteins

Subject Areas: Biology and Bio-materials, Medicine

Instruments: I02-Macromolecular Crystallography

Added On: 15/01/2014 13:06

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