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Issue 20, 2019
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A biocatalytic redox cascade approach for one-pot deracemization of carboxyl-substituted tetrahydroisoquinolines by stereoinversion

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Abstract

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 D-amino acid oxidase from Fusarium solani M-0718 (FsDAAO) 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 Δ1-piperidine-2-carboxylate/Δ1-pyrrolidine-2-carboxylate reductase from Pseudomonas putida KT2440 (PpDpkA) as a biocatalyst, yielding the corresponding (S)-1-carboxyl-substituted tetrahydroisoquinolines with high conversions and enantiomeric excess (>99% ee). By combining FsDAAO and PpDpkA 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 (S)-enantiomers with >99% conversions and >99% ee. Furthermore, preparative-scale biotransformation of racemic 1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid gave the (S)-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.

Graphical abstract: A biocatalytic redox cascade approach for one-pot deracemization of carboxyl-substituted tetrahydroisoquinolines by stereoinversion

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Publication details

The article was received on 08 Aug 2019, accepted on 06 Sep 2019 and first published on 10 Sep 2019


Article type: Paper
DOI: 10.1039/C9GC02795E
Green Chem., 2019,21, 5579-5585

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    A biocatalytic redox cascade approach for one-pot deracemization of carboxyl-substituted tetrahydroisoquinolines by stereoinversion

    S. Ju, M. Qian, J. Li, G. Xu, L. Yang and J. Wu, Green Chem., 2019, 21, 5579
    DOI: 10.1039/C9GC02795E

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