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Chemoenzymatic Approach to ( S )‐1,2,3,4‐Tetrahydroisoquinoline Carboxylic Acids Employing D‐Amino Acid Oxidase
Author(s) -
Ju Shuyun,
Qian Mingxin,
Xu Gang,
Yang Lirong,
Wu Jianping
Publication year - 2019
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201900178
Subject(s) - chemistry , tetrahydroisoquinoline , kinetic resolution , enantiomer , enantiomeric excess , carboxylic acid , d amino acid oxidase , enantioselective synthesis , combinatorial chemistry , stereochemistry , organic chemistry , oxidase test , catalysis , enzyme
Optically pure 1,2,3,4‐tetrahydroisoquinoline carboxylic acids constitute an important class of building blocks for the synthesis of natural products and synthetic pharmaceuticals. However, redox deracemization of racemic 1,2,3,4‐tetrahydroisoquinoline carboxylic acids as an attractive method is still challenging for the lack of suitable oxidoreductases. Herein, a D‐amino acid oxidase from Fusarium solani M‐0718 ( Fs DAAO) with broad substrate scope and excellent enantioselectivity was exploited through genome mining, and applied for the kinetic resolution of a number of racemic 1‐ and 3‐carboxyl substituted tetrahydroisoquinolines to yield the corresponding ( S )‐enantiomers with excellent enantiomeric excess ( ee ) values (up to >99%). By using Fs DAAO in combination with ammonia‐borane in one pot, deracemization of these racemic carboxyl‐substituted tetrahydroisoquinolines was achieved with conversions up to >98% and >99% ee . Preparative‐scale deracemization of racemic 1,2,3,4‐tetrahydroisoquinoline‐1‐carboxylic acid and 1,2,3,4‐tetrahydroisoquinoline‐3‐carboxylic acid was also demonstrated with good isolated yields (82% and 73%, respectively) and ee >99%. Our study provides an effective method for the synthesis of enantiomeric pure 1,2,3,4‐tetrahydroisoquinoline carboxylic acids. This method is expected to provide access to chiral carboxyl‐substituted 1,2,3,4‐tetrahydroquinolines and 1,2,3,4‐tetrahydro‐ß‐carbolines.