Hydrogenation involved in the chemical–biological synthesis of miglitol: effect of biological impurities on catalytic activity and catalyst reuse

BACKGROUND Miglitol is a potent alpha-glucosidase inhibitor that is used as a hypoglycemic agent. The industrial synthesis route of miglitol involves the biotransformation from N -2-hydroxyethyl glucamine to 6-( N -hydroxyethyl)-amino-6-deoxy-alpha- l -sorbofuranose and the subsequent hydrogenation from 6-( N -hydroxyethyl)-amino-6-deoxy-alpha -l- sorbofuranose to miglitol. This study comprehensively investigated the hydrogenation process and catalyst, and the effect of operating parameters on the product yield. RESULTS A 55.6% miglitol yield was obtained under the following optimal reaction conditions: 5 g L −1 palladium/carbon (Pd/C) (5% Pd); ethanol addition 1:1 ethanol:water (v/v); 80 g L −1 6-( N -hydroxyethyl)-amino-6-deoxy-alpha -l- sorbofuranose; reaction temperature 25 °C; solution pH 6; stirring speed 500 rpm; hydrogen pressure 1 MPa. The yield obtained was much higher than the average 36.8% in current industrial production. Catalyst deactivation during reuse was found to be caused by biological impurities, especially the macromolecular impurities introduced in previous biotransformation. The deposition of impurities on the porous support of the Pd/C catalyst may be the direct cause of catalyst deactivation. CONCLUSION Optimal conditions for the hydrogenation in the synthesis of miglitol were determined. It also was confirmed that biological impurities need to be completely removed to avoid catalyst deactivation and to improve catalyst reusability.