Attention deficit hyperactivity disorder (ADHD) is a malignancy that affects 3-5% of children in preschool age in The United States. Modafinil, (Attenace^®) is a non-addictive alternative for the treatment of ADHD in children. The R-isomer of Modafinil is marketed as Nuvigil^® for the treatment of excessive daytime sleepiness and Shift Work Sleep Disorder (SWSD). Moreover, Adrafinil (Olmifon^®) is currently in phase III clinical trials for the treatment of narcolepsy. The preparation of modafinil isomers is lead by the increasing interest in study the pharmacological differences of modafinil isomers and their implicancies in other diseases.

Modafinil contains a chiral sulfoxide and a carboxylic acid functionality. We prepared enantiomerically pure modafinil and adrafinil via separation of diastereomeric thiazolidinethione derivatives and determined the absolute configuration by X-ray crystallographic analysis. Although, there are several chemical methods for the preparation of chiral sulfoxides, stereoselective sulfoxidation using whole microorganisms has the advantage of being an environmentally low impact process. Stereoselective sulfoxidation of a b-sulfanyl acid using the fungus Beauveria bassiana allowed the preparation of S-sulfinyl acid in very good yield and exquisite enantioselectivity. Amidation of the corresponding S-sulfinyl acid with Bacillus subtilis furnished S-modafinil. We also found that the actinomycete Amycolatopsis orientalis transformed b-sulfanyl acid into rac-modafinil in a remarkable one-pot sulfoxidation/amidation reaction.