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Microbial metabolism of 2‐arylpropionic acids: Chiral inversion of ibuprofen and 2‐phenylpropionic acid
Author(s) -
Hutt Andrew J.,
Kooloobandi Azam,
Hanlon Geoffrey W.
Publication year - 1993
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.530050806
Subject(s) - metabolite , chemistry , enantiomer , metabolism , incubation , stereochemistry , stereoselectivity , biotransformation , substrate (aquarium) , chromatography , biochemistry , enzyme , catalysis , biology , ecology
Abstract 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. © 1993 Wiley‐Liss, Inc.