초록
<P>Halogenated derivatives of phenylalanine can be used as cross-coupling reagents for making drug-like molecules, and pure enantiomers of these precursors are therefore highly desirable. In our exploration of enzymatic routes to simplify the deracemisation process, the application of two enzymes, <SMALL>D</SMALL>-amino acid transaminase and phenylalanine dehydrogenase, both from <I>Lysinibacillus sphaericus</I>, has given promising results for the stereo-inversion of <SMALL>D</SMALL>-enantiomers of <I>para</I>-bromophenylalanine as the model substrate and also <I>p</I>-chloro/fluorophenylalanine and tyrosine. The addition of a coenzyme recycling system using ethanol and alcohol dehydrogenase reduced the amount of coenzyme needed for the reaction catalysed by phenylalanine dehydrogenase, reducing cost and permitting efficient and complete conversion of the racemic amino acids to the <SMALL>L</SMALL>-enantiomer. Relative proportions of the enzymes were optimized. The high purity of the <SMALL>L</SMALL>-enantiomer, with an ee over 99%, and the ease of the process make it an ideal alternative for deracemisation of the studied compounds.</P><P>Graphic Abstract</P><P><SMALL>D</SMALL>-Amino acid transaminase plus mutant phenylalanine dehydrogenase offer an effective one-pot system for 100% conversion of <SMALL>DL</SMALL>-amino acids to the <SMALL>L</SMALL>-form.<BR/><IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c6gc01922f'/><BR/></P>