Enantioselective synthesis of (S)-2-hydroxypropanone derivatives by benzoylformate decarboxylase catalyzed C-C bond formation

Chiral 2-hydroxypropanone derivatives 5a-v, 8a-d, and 10a, b were formed by benzoylformate decarboxylase (BFD) catalyzed C-C bond formation. A donor a ldehyde and acetaldehyde as an acceptor were carboligated in aqueous buffer solution with remarkable ease in high chemical yield and good to high opti cal purity. The substrate range of this thiamin diphosphate dependent enzym e was examined to employ this benzoin condensation type reaction in stereos elective synthesis. The observed dependence of the enantiomeric excess on t he substitution pattern could be exploited to design substrates resulting i n high selectivity Best substrates with regard to optical purity were meta- substituted benzaldehyde derivatives. To enable a general and convenient ap plicability of the BFD-catalyzed C-C bond formation, analytical batch exper iments were scaled up to give (S)-2-hydroxy ketones in good to high yields on a preparative scale. Further, the solubility of some of the organic subs trates in aqueous solution was increased by the use of cyclodextrin or buff er/DMSO mixtures.