19F NMR study on the biological Baeyer-Villiger oxidation of acetophenones.
The biological Baeyer-Villiger oxidation of acetophenones was studied by 19F nuclear magnetic resonance (NMR). The 19F NMR method was used to characterise the time-dependent conversion of various fluorinated acetophenones in either whole cells of Pseudomonas fluorescens ACB or in incubations with purified 4'-hydroxyacetophenone monooxygenase (HAPMO). Whole cells of P. fluorescens ACB converted 4'-fluoroacetophenone to 4-fluorophenol and 4'-fluoro-2'-hydroxyacetophenone to 4-fluorocatechol without the accumulation of 4'-fluorophenyl acetates. In contrast to 4-fluorophenol, 4-fluorocatechol was further degraded as evidenced by the formation of stoichiometric amounts of fluoride anion. Purified HAPMO catalysed the strictly NADPH-dependent conversion of fluorinated acetophenones to fluorophenyl acetates. Incubations with HAPMO at pH 6 and 8 showed that the enzymatic Baeyer-Villiger oxidation occurred faster at pH 8 but that the phenyl acetates produced were better stabilised at pH 6. Quantum mechanical characteristics explained why 4'-fluoro-2'-hydroxyphenyl acetate was more sensitive to base-catalysed hydrolysis than 4'-fluorophenyl acetate. All together, 19F NMR proved to be a valid method to evaluate the biological conversion of ring-substituted acetophenones to the corresponding phenyl acetates, which can serve as valuable synthons for further production of industrially relevant chemicals.
Moonen
M J
MJ
Laboratory of Biochemistry, Wageningen University, The Netherlands.
Rietjens
I M
IM
van Berkel
W J
WJ
D000098:Acetophenones / Q000378:metabolism*; D005461:Fluorine; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D010084:Oxidation-Reduction; D010105:Oxygenases / Q000378:metabolism; D011551:Pseudomonas fluorescens / Q000201:enzymology* / Q000254:growth & development
D000098:Acetophenones; D005461:Fluorine; D010105:Oxygenases; C427385:4-hydroxyacetophenone monooxygenase