Dynamic Kinetic Resolution of Ethyl 1,2,3,4‐Tetrahydro‐β‐carboline‐1‐carboxylate: Use of Different Hydrolases for Stereocomplementary Processes

Both enantiomers of 1,2,3,4‐tetrahydro‐β‐carboline‐1‐carboxylic acid have been prepared by dynamic kinetic resolution of the corresponding ethyl ester (±)‐1. CAL‐B‐catalysed hydrolysis of (±)‐1·HCl in NH4OAc buffer (pH 8.0, 30 °C) provided amino acid (R)‐2·HCl with 98 % ee and 90 % yield in 20 min. The hydrolysis with Alcalase in borate buffer (pH 8.0, 30 °C) showed S selectivity and the product (S)‐2·HCl was obtained with 60 % ee and 66 % yield in 45 h. The absolute configuration of (S)‐2 was determined by TDDFT electronic circular dichroism and optical rotation calculations. Directed dynamic kinetic enzymatic strategies have been developed for the preparation of both enantiomers of 1,2,3,4‐tetrahydro‐β‐carboline‐1‐carboxylic acid by the hydrolysis of ethyl 1,2,3,4‐tetrahydro‐β‐carboline‐1‐carboxylate. CAL‐B‐catalysed DKR gave the R enantiomer with an ee of 98 % and yield of 90 %. Alcalase‐catalysed DKR afforded the S enantiomer with an ee of 60 % and yield of 66 %.