FREE LIPASES-BASED ENZYMATIC ACETYLATION OF RACEMIC ATENOLOL: A PRELIMINARY KINETIC RESOLUTION STUDY

摘要

Since distomers of racemic drugs are frequently not used to heal diseases, utilization of single enantiomeric drugs not only decreases the drugs dosages and side effects but also reduces eco-toxicological problem. Since enzymatic membrane reactors (EMR) can be run continuously, observation on free-enzyme catalysis as a preliminary study before development of the EMR is needed. This paper describes acetylation of the racemic atenolol enzymatically using free lipases. The atenolol enantiomers reacted with vinyl acetate in water miscible organic compounds and phosphate buffer solutions. High conversions were obtained once the reactions were conducted in the organic media using PFL (XR: 84.22%, XS: 91.78%), Lipoprotein 62336 (XR: 100%; XS: 100%) and CALB (XR: 77%, XS: 51.82%). Reactions in PO4 buffers produced low conversions. It seems the KR process was difficult to be developed through the acetylation pathway. During observations on the AT enantiomers’ concentrations, the analytical protocols produced excellent selectivities. The highest selectivity was given by the slowest flow rate, which developed higher enantiomeric peak areas.