Oxidative and reductive transformations of epothilone A.
The C7 hydroxy group of cytotoxic epothilone A was selectively oxidized using PDC. A selective oxidation of the C3 hydroxy group was accomplished with Me2S/(PhCO2)2 after in situ protection of C7-OH. Reduction of epothilone A or of a C5, C7 dioxo derivative with NaBH4 proceeded at the C5 carbonyl group. Oxidation and hydrogenation of the C16-C17 double bond proved to be difficult but it was easily cleaved with ozone and the resulting keto derivative was transformed to epothilone analogs with different side chains.
Sefkow
M
M
Gesellschaft für Biotechnologische Forschung mbH, Abt. Naturstoffchemie, Braunschweig, Germany. sefkow@rz.uni-potsdam.de
Kiffe
M
M
Schummer
D
D
Höfle
G
G
D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D034261:Epothilones; D004852:Epoxy Compounds / Q000138:chemical synthesis*; D005285:Fermentation; D010084:Oxidation-Reduction; D013844:Thiazoles / Q000138:chemical synthesis*
D000970:Antineoplastic Agents; D034261:Epothilones; D004852:Epoxy Compounds; D013844:Thiazoles; C093787:epothilone A