Efficient dynamic kinetic resolution method for the synthesis of enantiopure 6-hydroxy- and 6-methoxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid

• Published in: Tetrahedron: Asymmetry
• Main Authors: Forró Enikő, Megyesi Rita, Paál Tihamér A., Fülöp Ferenc
• Format: Article in Journal/Newspaper
• Language: English
• Published: 2016
• Subjects: Antarc*; Antarctica
• Online Access: http://publicatio.bibl.u-szeged.hu/10568/; http://publicatio.bibl.u-szeged.hu/10568/1/forro_tet.pdf; https://doi.org/10.1016/j.tetasy.2016.10.011

Abstract Enantiomeric 6-hydroxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid (ee >99%), useful in the synthesis of modulators of nuclear receptors, including liver X receptor and its analogue 6-methoxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid (ee >99%), a source of the above enantiomer was synthesized through Candida antarctica lipase B-catalysed dynamic kinetic hydrolysis of the corresponding 1,2,3,4-tetrahydroisoquinoline-1-carboxylic esters (±)-4·HCl and (±)-5. (R)-Selective hydrolysis in both organic solvents and an aqueous NH4OAc buffer at pH 8.5 was observed and the amino acids were obtained in good chemical yields (>87%).