Microbial oxidation/amidation of benzhydrylsulfanyl acetic acid. Synthesis of (+)-modafinil

A highly enantioselective oxidation of benzhydrylsulfanyl acetic acid to the corresponding (S)-sulfinyl carboxylic acid was achieved employing the fungus Beauveria bassiana in very good yield. This product was amidated using the bacteria Bacillus subtilis to afford (S)-modafinil in good yield.

Figure optionsDownload as PowerPoint slide

(+)-(S)-(Diphenylmethanesulfinyl)acetic acidC15H14O3S[α]D22 = +38.3 (c 1.0, CH3OH)Ee: 99% (chiral HPLC)Absolute configuration: SsSource of chirality: microbial oxidation

(+)-(S)-(Diphenylmethanesulfinyl)acetamideC15H15NO2S[α]D22 = +79 (c 1.0, CHCl3)Ee: 100% (chiral HPLC)Absolute configuration: SsSource of chirality: [(4R)-Phenyl-2-thioxo-thiazolidine-3-yl]-(S)-(diphenylmethanesulfinyl)acetamide