초록
<P>Optically pure 1,2,3,4-tetrahydroisoquinoline carboxylic acids are important chiral building blocks in the pharmaceutical and fine chemical industries. However, the existing chemo-enzymatic deracemization method employing <SMALL>D</SMALL>-amino acid oxidase from <I>Fusarium solani</I> M-0718 (<I>Fs</I>DAAO) suffers from the requirement for a large excess of a nonselective chemical reducing agent. To explore an alternative method, we envisaged a concurrent biocatalytic oxidation and reduction cascade in one pot. Herein, we report a novel biocatalytic route for the asymmetric reduction of 3,4-dihydroisoquinoline-1-carboxylic acids employing Δ<SUP>1</SUP>-piperidine-2-carboxylate/Δ<SUP>1</SUP>-pyrrolidine-2-carboxylate reductase from <I>Pseudomonas putida</I> KT2440 (<I>Pp</I>DpkA) as a biocatalyst, yielding the corresponding (<I>S</I>)-1-carboxyl-substituted tetrahydroisoquinolines with high conversions and enantiomeric excess (>99% ee). By combining <I>Fs</I>DAAO and <I>Pp</I>DpkA in one pot, a fully biocatalytic method was demonstrated for the deracemization of a range of racemic 1-carboxyl substituted tetrahydroisoquinolines to produce the corresponding (<I>S</I>)-enantiomers with >99% conversions and >99% ee. Furthermore, preparative-scale biotransformation of racemic 1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid gave the (<I>S</I>)-enantiomer with 89% isolated yield and >99% ee. Taken together, we provide an enantioselective biocatalytic redox cascade method for the one-pot synthesis of enantiopure 1,2,3,4-tetrahydroisoquinoline carboxylic acids.</P><P>Graphic Abstract</P><P>We describe a biocatalytic redox cascade reaction for one-pot enantioselective synthesis of (<I>S</I>)-carboxyl substituted tetrahydroisoquinolines.<BR/><IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c9gc02795e'/><BR/></P>