Synthetic ansamycins prepared by a ring-expanding Claisen rearrangement. Synthesis and biological evaluation of ring and conformational analogues of the Hsp90 molecular chaperone inhibitor geldanamycin

Christopher S. P. McErlean, Nicolas Proisy, Christopher J. Davis, Nicola A. Boland, Swee Y. Sharp, Kathy Boxall, Alexandra M. Z. Slawin, Paul Workman, Christopher J. Moody

Research output: Contribution to journalReview articlepeer-review

17 Citations (Scopus)

Abstract

A series of ansa-quinones has been prepared by chemical synthesis, and evaluated by biological techniques. Thus, 19-membered ansa-lactams, simplified analogues of the naturally occurring Hsp90 molecular chaperone inhibitor geldanamycin, were obtained by concise routes, the key steps being the combination of a ring-closing metathesis to give a 17-membered ring followed by Claisen rearrangement to effect ring expansion. The methodology was also used to prepare an "unnatural" 18-membered ring analogue. In ATPase enzyme assays, the synthetic ansa-quinones were weak inhibitors of Hsp90.

Original languageEnglish
Pages (from-to)531-546
Number of pages16
JournalOrganic & Biomolecular Chemistry
Volume5
DOIs
Publication statusPublished - 2007

Keywords

  • POTENT HEAT-SHOCK-PROTEIN-90 INHIBITORS
  • BRIDGED MACROCYCLIC LACTAMS
  • PROTEIN-FOLDING MACHINERY
  • GLYCOLATE ALDOL REACTIONS
  • SOLID-SUPPORTED REAGENTS
  • STRUCTURE-BASED DESIGN
  • IN-VITRO
  • CLOSING METATHESIS
  • CRYSTAL-STRUCTURE
  • PHENOL OXIDATION

Fingerprint

Dive into the research topics of 'Synthetic ansamycins prepared by a ring-expanding Claisen rearrangement. Synthesis and biological evaluation of ring and conformational analogues of the Hsp90 molecular chaperone inhibitor geldanamycin'. Together they form a unique fingerprint.

Cite this