Microbial metabolism of 2-arylpropionic acids: chiral inversion of ibuprofen and 2-phenylpropionic acid.
The metabolism of (R,S)-ibuprofen has been investigated in 24 microbial cultures. Of these Cunninghamella elegans, Mucor hiemalis, and Verticillium lecanii catalyzed the oxidation of the drug to 2-[4-(2-hydroxy-2-methylpropyl)phenyl]propionic acid, a known mammalian metabolite. The extent of metabolism was greatest with V. lecanii, with some 47% of the substrate being consumed over a 7-day incubation period. Enantiomeric analysis indicated stereoselective metabolism of (R)-ibuprofen, the enantiomeric composition of the residual substrate being R/S = 0.25. Following a preparative scale incubation of (R,S)-ibuprofen with V. lecanii, in which the reaction was allowed to go to completion, the metabolite was found to be predominantly of the S-configuration (S/R = 2.1), suggesting that chiral inversion of either the drug and/or the metabolite had taken place. Analysis of extracts following incubation of (R,S)-, (R)-, and (S)-2-phenylpropionic acid with V. lecanii, for 21 days, indicated that chiral inversion of the (R)-enantiomer to its optical antipode had taken place. The results of these investigations indicate that microorganisms, in addition to mammals, are able to mediate the chiral inversion of 2-arylpropionic acids. This observation may have implications for the preparation of optically pure 2-arylpropionic acids.
Hutt
A J
AJ
Department of Pharmacy, King's College London, United Kingdom.
Kooloobandi
A
A
Hanlon
G W
GW
D007052:Ibuprofen / Q000737:chemistry / Q000378:metabolism*; D003904:Mitosporic Fungi / Q000378:metabolism*; D009089:Mucor / Q000378:metabolism*; D009090:Mucorales / Q000378:metabolism*; D010666:Phenylpropionates / Q000737:chemistry / Q000378:metabolism*; D012189:Retrospective Studies; D013237:Stereoisomerism
D010666:Phenylpropionates; C013025:hydratropic acid; D007052:Ibuprofen