Chemoenzymatic preparation of optically active 4-aryl-5-carboxy-6-methyl-3,4-dihydro-2(1H)-pyridone derivatives

Abstract A series of racemic 4-aryl-5-( tert -butoxycarbonyl)-6-methyl-3,4-dihydro-2(1 H )-pyridones have been prepared by means of a modified Hantzsch reaction using commercially available starting materials. An easy removal of the tert -butyl group of these pyridones and subsequent reaction with cesium carbonate and chloromethyl 2-methylpropanoate provided us suitable substrates (±)- 5 to be used in lipase-catalyzed hydrolysis reactions. Lipase B from Candida antarctica (CAL-B) was the most adequate lipase in the hydrolysis of (±)- 5 . Despite the low enantioselectivity values obtained ( E ≤12), several optically active pyridone derivatives were finally isolated with high enantiomeric excesses (ee≥91%) and moderate yields.