Microbial Hydroxylation and Simultaneous Formation of the 4''-O-Methylglucoside of the Tyrosine-Kinase Inhibitor CGP 62706

Abstract

Two fungal strains of Beauveria bassiana, DSM 875 and DSM 1344, hydroxylated CGP 62706, an inhibitor of the EGF-receptor tyrosine kinase, in the C(4') position and subsequently formed the glucosylated metabolite with 5–11% and 7–15% yield, respectively. The reaction could be successfully scaled up to 3 l fermentation volume with strain DSM 875. The structure of the glycosylated compound was determined by micro-HPLC-MS and NMR after production by fermentation on the mg scale. In addition, the biotransformation also provides access to the free 4'-hydroxylated compound, as the glycoside can easily be hydrolyzed.