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Synfacts 2006(6): 0606-0606  
DOI: 10.1055/s-2006-941782
Bioorganic Chemistry and Organocatalysis
© Georg Thieme Verlag Stuttgart · New York

Biocatalyzed α-Hydroxylation of Phenyl-acetic Acid Derivatives and Buspirone

Contributor(s): Benjamin List, Nolwenn J. A. Martin
M. Landwehr, L. Hochrein, C. R. Otey, A. Kasrayan, J.-E. Bäckvall, F. H. Arnold*
California Institute of Technology, Pasadena, USA; Stockholm University, Sweden
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Publication History

Publication Date:
19 May 2006 (online)

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Significance

Herein, an interesting new enantio­selective, biocatalytic route to (S)-mandelic acid derivatives 2 via direct α-hydroxylation of phenyl­acetic acid esters 1, catalyzed by engineered microbial cytochrome P450 BM-3 (CYP102A subfamily), is described. The size of the ester group influences binding and specificity of the reaction. By varying the chain length of the ester, the catalyst selectivity can be improved. This biocatalytic method has also been successfully applied to the α-hydroxylation of the imide portion of buspirone 3 to synthesize its authentic human metabolite, (R)-6-hydroxybuspirone 4, with excellent enantio­selectivity (99.5% ee).