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 and Moody, Chrisostomos (2014) Synthesis of macrolactam analogues of radicicol and their binding to heat shock protein Hsp90. Organic and Biomolecular Chemistry, 12 (8). pp. 1328-1340. ISSN 1477-0520

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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. © 2014 The Royal Society of Chemistry.

Item Type: Article
Schools and Departments: School of Life Sciences > Chemistry
Subjects: Q Science > QD Chemistry
Depositing User: Tom Gittoes
Date Deposited: 05 Mar 2015 14:14
Last Modified: 05 Mar 2015 14:14
URI: http://sro.sussex.ac.uk/id/eprint/53232
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