PEG600-carboxylates as acylating agents for the continuous enzymatic kinetic resolution of alcohols and amines

Abstract

Enantiomerically pure alcohols and amines are important building blocks for the pharmaceutical and agrochemical industries. Among the different approaches to reach these compounds, enzyme-catalyzed kinetic resolution (EKR) of racemates is one of the most widely studied and employed methodologies. In this kind of reaction, the acyl donor plays an important role, making the search for new acylating agents an attractive field. Herein, we report our results over the use of PEG600 carboxylates as acylating agent for separation of amines and alcohols enantiomers in continuous flow. For the EKR of 1-phenylethylamine, PEG600-diester show the best results, and (S)-1-phenylethylamine was obtained with high yield and enantiomeric purity (49% yield and >99% (S)) with a productivity of 211 mg h−1 genzyme−1. (R)-1-phenylethylamine was recovered after chemical hydrolysis of the amide formed with high yield and ee (35% yield and 95% ee). In addition, the immobilized enzyme remains active for at least 20 h operation. On the other hand, (R)- and (S)-1-phenylethanol was obtained after continuous lipase-catalyzed hydrolysis of the ester (formed after reaction with PEG) in good conversions to both enantiomers, with a productivity of 68 mg h−1 g enzyme−1 for the (S)- enantiomer and 64 mg h−1 genzyme−1 for the (R) enantiomer.