Format:
Online-Ressource
ISSN:
1521-3765
Content:
Abstract: A series of resorcylic acid macrolactones, analogues of the natural product radicicol has been prepared by chemical synthesis, and evaluated as inhibitors of heat shock protein 90 (Hsp90), an emerging attractive target for novel cancer therapeutic agents. The synthesis involves acylation of an ortho‐toluic acid dianion, esterification, followed by a ring‐closing metathesis to form the macrocycle. Subsequent manipulation of the protected hydroxymethyl side chain allows access to a range of new analogues following deprotection of the two phenolic groups. Co‐crystallization of one of the new macrolactones with the N‐terminal domain of yeast Hsp90 confirms that it binds in a similar way to the natural product radicicol and to our previous synthetic analogues, but that the introduction of the additional hydroxymethyl substituent appears to result in an unexpected change in conformation of the macrocyclic ring. As a result of this conformational change, the compounds bound less favorably to Hsp90.
In:
volume:16
In:
number:34
In:
year:2010
In:
pages:10366-10372
In:
extent:7
In:
Chemistry - a European journal, Weinheim : Wiley-VCH, 1995-, 16, Heft 34 (2010), 10366-10372 (gesamt 7), 1521-3765
Language:
English
DOI:
10.1002/chem.201001119
URN:
urn:nbn:de:101:1-2023041106092058019029
URL:
https://doi.org/10.1002/chem.201001119
URL:
https://nbn-resolving.org/urn:nbn:de:101:1-2023041106092058019029
URL:
https://d-nb.info/1285880285/34
URL:
https://doi.org/10.1002/chem.201001119