Bioconversion of aminophosphonates to hydroxyphosphonates via two step redox reactions employing fungi

摘要

The conversion path and the complex procedure of products separation elaborated for ketophosphonates and hydroxyphosphonates formed during the biotransformations of aminophoshonates are reported. Penicillium funiculosum (Thom 3), Geotrichum candidum (6593), Beauveria bassiana (271B) were applied for bioconversion of a racemic mixture of the phosphonic analogue of isoleucine (Ile(P)), whereas P. funiculosum (Thom 3), F. oxysporum (DSM 12646) and Trigonopsis variabilis (DSM 70714) were used for transformation of the phosphonic analogue of valine (Val(P)). The biocatalytic processes were analysed to confirm and to compare the path and the selectivity of the biological conversion of aminophosphonates with one (Val(P)) and two stereogenic centers (Ile(P)). The efforts undertaken allowed to demonstrate, that applied biocatalysts act in two steps. A racemic mixture of substrates was bioconverted via oxidative deamination with formation of ketones, which were subsequently bioreduced in the next step of the process. As it was proved the selectivity of the bioreactions differs depending on the structure of the substrate. The first step of the process in the case of the phosphonic analogue of valine 4 allowed to obtain the pure unreacted enantiomer of aminophosphonate (R) whereas the biotransformation of Ile(P) was unselective. Both ketone intermediates were reduced in a non-selective way. The results were evaluated by NMR, MS and IR techniques, which confirmed the path of the biocatalytic two steps redox reaction: oxidation and reduction.