The stereo inversion of 2-arylpropionic acid non-steroidal anti-inflammatory drugs and structurally related compounds by Verticillium lecanii.
The fungus Verticillium lecanii has previously been shown to be capable of inverting the chirality of ibuprofen and 2-phenylpropionic acid from the (R)-enantiomer to the corresponding (S)-antipode, a phenomenon also observed in mammalian systems including man. An investigation is reported here into the substrate specificity of the enzyme system present in V. lecanii using the following 2-arylpropionic acids: ibuprofen, ketoprofen, indoprofen, suprofen, flurbiprofen and fenoprofen, together with the structurally related compounds 2-phenylbutyric acid, 2-phenoxypropionic acid, mandelic acid, atrolactic acid, etodolac and alpha-methoxyphenylpropionic acid. The results demonstrated that V. lecanii is capable of inverting the chirality of all the 2-arylpropionic acids investigated. All were inverted in the (R) to (S) direction with the exception of ketoprofen, where inversion was observed in the reverse direction. Using the structurally related compounds as substrates, the size of the alkyl substitutent at the alpha-carbon at the methyl group, and the presence of the methyl group at the chiral centre, were found to be critical. These results suggest that V. lecanii could be used as a basis for the production of pure enantiomers of the 2-arylpropionic acids in commercial biotransformations.
Thomason
M J
MJ
Department of Pharmacy, University of Brighton, UK.
Rhys-Williams
W
W
Lloyd
A W
AW
Hanlon
G W
GW
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003904:Mitosporic Fungi / Q000378:metabolism*; D011422:Propionates / Q000737:chemistry / Q000378:metabolism*; D013237:Stereoisomerism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011422:Propionates