Method for preparing a pharmaceutically active enantiomeric or enantiomerically enriched sulfoxide compound by enantioselective bioreduction of a racemate sulfoxide compound

A method of obtaining a pharmaceutically active compound as a single sulfoxide enantiomer or an enantiomerically enriched sulfoxide form having the formula (II):

• ##STR14## wherein:
• ##STR15## and ##STR16## and ##STR17## wherein:
• N in the benzimidazole moiety of Het.sub.2 means that one of the carbon atoms substituted by any one of R.sub.6 to R.sub.9 is exchanged for an unsubstituted nitrogen atom;
• R.sub.1, R.sub.2 and R.sub.3 are the same or different and selected from the group consisting of hydrogen, alkyl, alkoxy which is unsubstituted or substituted by fluorine, alkylthio, alkoxyalkoxy, dialkylamino, piperidino, morpholino, halogen, phenylalkyl and phenylalkoxy;
• R.sub.4 and R.sub.4 are the same or different and selected from the group consisting of hydrogen, alkyl and aralkyl;
• R.sub.5 is hydrogen, halogen, trifluoromethyl, alkyl or alkoxy;
• R.sub.6 -R.sub.9 are the same or different and selected from the group consisting of hydrogen, alkyl, alkoxy, halogen, haloalkoxy, alkylcarbonyl, alkoxycarbonyl, oxazolyl and trifluoroalkyl;
• or adjacent groups among substituents R.sub.6 -R.sub.9 together with the carbon atoms to which they are attached form an unsubstituted or a substituted ring;
• R.sub.10 is hydrogen or alkoxycarbonyloxymethyl;
• R.sub.11 is hydrogen or forms an alkylene chain together with R.sub.3 ;
• R.sub.12 and R.sub.13 are the same or different and selected from the group consisting of hydrogen, halogen and alkyl;
• which method comprises the steps of:
• enantioselectively bioreducing a racemic sulfoxide compound of the formula (II) to the corresponding sulfide compound of formula (I):
• Het.sub.1 -X-S-Het.sub.2 (I)
• by means of a microbial organism or a microbial enzyme system;
• and
• isolating the pharmaceutically active single enantiomeric or enantiomerically enriched sulfoxide compound.