(438c) Enantioselective Synthesis of (S)-1,2,3,4-Tetrahydroisoquinoline Carboxylic Acids Via D-Amino Acid Oxidase Mediated Chemo-Enzymatic Cascade Reaction
AIChE Annual Meeting
Wednesday, November 13, 2019 - 8:36am to 8:54am
Herein, a D-amino acid oxidase from Fusarium solani M-0718 (FsDAAO) with broad substrate scope and excellent enantioselectivity was exploited through genome mining. It was applied in the kinetic resolution of a number of racemic 1- and 3-carboxyl substituted THIQs with different substitutions on the phenyl ring to yield the corresponding (S)-enantiomers with excellent ee (up to >99%) for the first time. By using FsDAAO in combination with ammonia-borane in one-pot, deracemization of these racemic carboxyl-substituted THIQs was achieved with conversions up to >98% and >99% ee. Noteworthily, preparative-scale deracemization of racemic 1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid and 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid was demonstrated with good yield (82% and 73%, respectively) and ee >99%. Our study provides a novel and general 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.