ENANTIOSELECTIVE PREPARATION OF PHARMACEUTICALLY ACTIVE SULFOXIDES BY BIOOXIDATION

摘要

A compound of formula (II) is prepared either as a single enantiomer or in an enantiomerically enriched form, wherein Het1 is (a) or (b) and Het2 is (c) or (d) and X is (e) or (f) wherein N in the benzimidazole moiety means that one of the carbon atoms substituted by R6-R9 optionally may be exchanged for an unsubstituted nitrogen atom; R1, R2 and R3 are the same or different and selected from hydrogen, alkyl, alkoxy optionally substituted by fluorine, alkylthio, alkoxyalkoxy, dialkylamino, piperidino, morpholino, halogen, phenylalkyl, phenylalkoxy; R4 and R4' are the same or different and selected from hydrogen, alkyl, aralkyl; R5 is hydrogen, halogen, trifluoromethyl, alkyl, alkoxy; R6-R9 are the same or different and selected from hydrogen, alkyl, alkoxy, halogen, haloalkoxy, alkylcarbonyl, alkoxycarbonyl, oxazolyl, trifluoroalkyl or adjacent groups R6-R9 may complete together with the carbon atoms to which they are attached optionally substitued ring structures; R10 is hydrogen or alkoxycarbonyloxymethyl; R11 is hydrogen or forms an alkylene chain together with R3; R12 and R13 are the same or different and selected from hydrogen, halogen or alkyl, by a method comprising stereoselective biooxidation of the pro-chiral sulfide counterpart compound.