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Propionate Analogues of Zearalenone Bind to Hsp90
Author(s) -
Ugele Markus,
Sasse Florenz,
Knapp Stefan,
Fedorov Oleg,
Zubriene Asta,
Matulis Daumantas,
Maier Martin E.
Publication year - 2009
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200900109
Subject(s) - chemistry , propionate , zearalenone , alkylation , stereochemistry , alkyne , geldanamycin , ring closing metathesis , hsp90 , depsipeptide , enantiomer , grignard reaction , metathesis , biochemistry , organic chemistry , mycotoxin , heat shock protein , catalysis , polymer , food science , polymerization , gene , reagent
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 μ M ) itself. In the thermal‐shift assay, two analogues 35 and ent ‐ 35 displayed stronger binding than the natural product geldanamycin to the chaperone Hsp90.