Synthesis of macrolactam analogues of radicicol and their binding to heat shock protein Hsp90
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 We...
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Royal Society of Chemistry
2014
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| Online Access: | https://eprints.nottingham.ac.uk/3299/ |
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| author | Dutton, Bridie L. Kitson, Russell R.A. Parry-Morris, Sarah Roe, S. Mark Prodromou, Chrisostomos Moody, Christopher J. |
| author_facet | Dutton, Bridie L. Kitson, Russell R.A. Parry-Morris, Sarah Roe, S. Mark Prodromou, Chrisostomos Moody, Christopher J. |
| author_sort | Dutton, Bridie L. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T18:21:29Z |
| format | Article |
| id | nottingham-3299 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T18:21:29Z |
| publishDate | 2014 |
| publisher | Royal Society of Chemistry |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-32992020-05-04T16:42:37Z https://eprints.nottingham.ac.uk/3299/ 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 Moody, Christopher J. 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. Royal Society of Chemistry 2014-02-28 Article PeerReviewed Dutton, Bridie L., Kitson, Russell R.A., Parry-Morris, Sarah, Roe, S. Mark, Prodromou, Chrisostomos and Moody, Christopher J. (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 http://pubs.rsc.org/en/Content/ArticleLanding/2014/OB/c3ob42211a#!divAbstract doi:10.1039/C3OB42211A doi:10.1039/C3OB42211A |
| spellingShingle | Dutton, Bridie L. Kitson, Russell R.A. Parry-Morris, Sarah Roe, S. Mark Prodromou, Chrisostomos Moody, Christopher J. Synthesis of macrolactam analogues of radicicol and their binding to heat shock protein Hsp90 |
| title | Synthesis of macrolactam analogues of radicicol and their binding to heat shock protein Hsp90 |
| title_full | Synthesis of macrolactam analogues of radicicol and their binding to heat shock protein Hsp90 |
| title_fullStr | Synthesis of macrolactam analogues of radicicol and their binding to heat shock protein Hsp90 |
| title_full_unstemmed | Synthesis of macrolactam analogues of radicicol and their binding to heat shock protein Hsp90 |
| title_short | Synthesis of macrolactam analogues of radicicol and their binding to heat shock protein Hsp90 |
| title_sort | synthesis of macrolactam analogues of radicicol and their binding to heat shock protein hsp90 |
| url | https://eprints.nottingham.ac.uk/3299/ https://eprints.nottingham.ac.uk/3299/ https://eprints.nottingham.ac.uk/3299/ |