A new chemoenzymatic approach to the synthesis of chiral 4-aryl-1,4-dihydro-2H-isoquinolines via the enzymatic resolution of 2-acetyl-4-phenyl-1,4-dihydro-2H-isoquinolin-3-one

A new chemoenzymatic method is proposed for the synthesis of enantiomerically pure 4-phenyl-1,4-dihydro-2H-isoquinolines based on the enzymatic kinetic resolution of 2-acetyl-4-phenyl-1,4-dihydro-2H-isoquinolin-3-one. For the enzymatic resolution of the racemic substrate, readily available ‘home made’ animal liver acetone powders (LAPs) were used. Excellent enantioselectivity, exceeding 500, was achieved in a short reaction time upon application of turkey liver acetone powder as the biocatalyst. Reduction of obtained product led to the formation of amine (R)-1, which is hardly available using standard procedures. These results show that N-acetyl lactams are a new type of substrate for enzymatic biotransformations.

Figure optionsDownload as PowerPoint slide

(4R)-4-Phenyl-1,4-dihydroisoquinolin-3(2H)-oneC15H13NO[α]D22 = −10.2 (c 1.0, CHCl3)Absolute configuration: (R)Source of chirality: enzymatic hydrolysis

(4R)-4-Phenyl-1,4-dihydro-2H-isoquinolineC15H15N[α]D22 = +1.2 (c 1.0, CH3OH)Absolute configuration: (R)Source of chirality: enzymatic hydrolysis