The stereo inversion of 2‐arylpropionic acid non‐steroidal anti‐inflammatory drugs and structurally related compounds by Verticillium lecanii

• Published in: Journal of applied microbiology 1998-07, Vol.85 (1), p.155-163
• Main Authors: THOMASON, M. J, RHYS-WILLIAMS, W, LLOYD, A. W, HANLON, G. W
• Format: Article
• Language: English
• Subjects: 2-Phenylpropionic acid; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - metabolism; Bioconversions. Hemisynthesis; Biological and medical sciences; Biotechnology; biotransformation; Chromatography, High Pressure Liquid; flurbiprofen; Fundamental and applied biological sciences. Psychology; hydrocinnamic acid; indoprofen; ketoprofen; Methods. Procedures. Technologies; Mitosporic Fungi - metabolism; Propionates - chemistry; Propionates - metabolism; stereo inversion; Stereoisomerism; suprofen; Verticillium lecanii
• ISSN: 1364-5072; 1365-2672
• DOI: 10.1046/j.1365-2672.1998.00483.x

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 α‐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 substituent at the α‐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.