Targeting the Hsp90 Chaperone: Synthesis of Novel Resorcylic Acid Macrolactone Inhibitors of Hsp90 |
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| Authors: | James E H Day Dr Swee Y Sharp Dr Martin G Rowlands Dr Wynne Aherne Dr Paul Workman Prof Dr Christopher J Moody Prof Dr |
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| Institution: | 1. School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD (UK), Fax: (+44)?115‐951‐3564;2. Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, Haddow Laboratories, 15 Cotswold Road, Sutton, Surrey, SM2 5NG (UK) |
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| Abstract: | A series of benzo‐macrolactones 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. A new synthesis of these resorcylic acid macrolactone analogues of the natural product radicicol is described in which the key steps are the acylation and ring opening of a homophthalic anhydride to give an isocoumarin, followed by a ring‐closing metathesis to form the macrocycle. The methodology has been extended to a novel series of macrolactones incorporating a 1,2,3‐triazole ring. |
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| Keywords: | anticancer agents cycloaddition enzyme inhibitors macrocyclic compounds metathesis |
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