Propionate analogues of zearalenone bind to Hsp90.
By replacement of an acetate with propionate through organic synthesis a range of zearalenone analogues were prepared. As key steps in the synthesis of the analogues we used the Noyori hydrogenation of methyl acetoacetate followed by Frater alkylation of the enantiomeric 3-hydroxybutyrates. This con...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2009
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| _version_ | 1826259349989752832 |
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| author | Ugele, M Sasse, F Knapp, S Fedorov, O Zubriene, A Matulis, D Maier, M |
| author_facet | Ugele, M Sasse, F Knapp, S Fedorov, O Zubriene, A Matulis, D Maier, M |
| author_sort | Ugele, M |
| collection | OXFORD |
| description | By replacement of an acetate with propionate through organic synthesis a range of zearalenone analogues were prepared. As key steps in the synthesis of the analogues we used the Noyori hydrogenation of methyl acetoacetate followed by Frater alkylation of the enantiomeric 3-hydroxybutyrates. This converted the second acetate to a propionate. Through the derived alkyne, chain extension led to 3-methylundec-10-en-2-ol derivatives. These were condensed with 2,4-dimethoxy-6-vinylbenzoic acid. Ring-closing metathesis of the obtained esters led to macrolactones, which were deproteced to give the zearalenone analogues. Several of the analogues showed cytotoxicity against the L929 mouse fibroblast cell line comparable to zearalenone (9 microM) itself. In the thermal-shift assay, two analogues 35 and ent-35 displayed stronger binding than the natural product geldanamycin to the chaperone Hsp90. |
| first_indexed | 2024-03-06T18:48:27Z |
| format | Journal article |
| id | oxford-uuid:0f5a4de4-eaf7-475d-b47c-e84259179209 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:48:27Z |
| publishDate | 2009 |
| record_format | dspace |
| spelling | oxford-uuid:0f5a4de4-eaf7-475d-b47c-e842591792092022-03-26T09:50:48ZPropionate analogues of zearalenone bind to Hsp90.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:0f5a4de4-eaf7-475d-b47c-e84259179209EnglishSymplectic Elements at Oxford2009Ugele, MSasse, FKnapp, SFedorov, OZubriene, AMatulis, DMaier, MBy replacement of an acetate with propionate through organic synthesis a range of zearalenone analogues were prepared. As key steps in the synthesis of the analogues we used the Noyori hydrogenation of methyl acetoacetate followed by Frater alkylation of the enantiomeric 3-hydroxybutyrates. This converted the second acetate to a propionate. Through the derived alkyne, chain extension led to 3-methylundec-10-en-2-ol derivatives. These were condensed with 2,4-dimethoxy-6-vinylbenzoic acid. Ring-closing metathesis of the obtained esters led to macrolactones, which were deproteced to give the zearalenone analogues. Several of the analogues showed cytotoxicity against the L929 mouse fibroblast cell line comparable to zearalenone (9 microM) itself. In the thermal-shift assay, two analogues 35 and ent-35 displayed stronger binding than the natural product geldanamycin to the chaperone Hsp90. |
| spellingShingle | Ugele, M Sasse, F Knapp, S Fedorov, O Zubriene, A Matulis, D Maier, M Propionate analogues of zearalenone bind to Hsp90. |
| title | Propionate analogues of zearalenone bind to Hsp90. |
| title_full | Propionate analogues of zearalenone bind to Hsp90. |
| title_fullStr | Propionate analogues of zearalenone bind to Hsp90. |
| title_full_unstemmed | Propionate analogues of zearalenone bind to Hsp90. |
| title_short | Propionate analogues of zearalenone bind to Hsp90. |
| title_sort | propionate analogues of zearalenone bind to hsp90 |
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