Preparation of pharmaceutically active compounds by biooxidation
AssigneeAstra Aktiebolag
InventorsRobert Holt, Per Lindberg, Christopher Reeve, Stephen Taylor
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Abstract
Enantiomeric or enantiomerically enriched H.sup.+ K.sup.+ ATPase inhibiting pyridinylsulfinyl--benzimidazoles are prepared using microorganisms or microbial enzyme systems to enantioselectively biooxidize corresponding prochiral sulfide compounds and isolating the pharmaceutically active enantiomer or enantiomerically enriched sulfoxide form.
Claims9
A method of preparing a pharmaceutically active compound as a single sulfoxide enantiomer or an enantiomerically enriched form having the formula (II) ##STR11## wherein Het.sub.1 is ##STR12## and Het.sub.2 is ##STR13## and X is ##STR14## 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.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 R.sub.6 -R.sub.9 together with the carbon atoms to which they are attached form an unsubstituted or substituted ring;
- R.sub.10 is hydrogen or alkoxycarbonyloxymethyl;
- R.sub.11 is hydrogen or forms an alkylene chain together with R.sub.3 ;
- which method comprises the steps of:
- enantioselectively biooxidizing a pro-chiral sulfide compound of the formula (I):
- Het1--X--S--Het2 (I)
- by means of a microbial organism or a microbial enzyme system;
- and
- isolating the pharmaceutically active single enantiomeric or enantiomerically enriched sulfoxide compound.
A method according to any one of the previous claims wherein a single enantiomer of the compound of formula (II) is prepared.
A method of preparing a pharmaceutically active compound as a single sulfoxide enantomer or an enantiomerically enriched form of formula (IIa):
- ##STR17## comprising the steps of:
- (a) enantioselectively bioxidizing the corresponding prochiral sulfide compound of formula (Ia):
- ##STR18## by means of the microbial organism Ustilago maydis or a microbial enzyme system isolated therefrom;
- and
- (b) isolating the pharmaceutically active single enantiomeric or enantiomerically enriched sulfoxide compound.
Dependencies are inferred from the claim text.