Study on chemoenzymatic synthesis of optically pure (S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid

The process to prepare optically pure (S)-l,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) by chemoenzymatic synthesis with racemic phenylalanine and polyformate as starting materials and hydrobromic acid as catalyst, through Pictet-Spengler reaction, esterification, and enzymatic hydrolysis by CRL lipase was introduced. The racemic Tic yield can reach 87.1% under the following optimal conditions of Pictet-Spengler reaction such as: at 60°C for 5 h with n(phenylalanine):n(polyformate):n(HBr)=1:1.4:8.8 (HBr is a 40% mass ratio as aqueous solution). The chemical yield can reach 49.1% with 99.5%(enantiomerically purity) of (S)-Tic under such optimal conditions of enzymatic hydrolytic reaction as the following: at 30°C for 48 h with a 0.20 of mass ratio between CRL enzyme and substrate under pH 7.5.