Process development of methylenedioxyphenyl-acetone chiral bioreduction

Talampanel is a non-competitive antagonist of AMPA receptor, and it is a drug studied for the treatment of epilepsy and cerebrovascular ischemia. The first step of an efficient synthesis of talampanel is the reduction of 3,4-methylenedioxyphenyl-acetone (MDA) to (S)-α-methyl-1,3-benzodioxole-5-ethanol (MBE) accomplished with the use of Zygosaccharomyces rouxii in the presence of XAD-7 resin. Z. rouxii was chosen for its resistance to higher substrate and product concentrations (<6 g/l) and its higher reductase activity in comparison to other yeasts. Application of the moderately polar adsorbent resulted in low and non-toxic concentration of both the substrate and product in water phase. cost fermentation medium without any component of animal origin was elaborated to produce Z. rouxii biomass. The control of pH and dissolved oxygen concentration, temperature, antifoam system, the time of harvest, the rate of inoculations and the number of inoculation steps were also studied. The fermentation process in 1000 l fermentor provided cell paste, possessing satisfactory ketoreductase activity (95–99%) with excellent enantioselectivity. od was developed to measure enzyme activity and to determine the key parameters of bioreduction. Excellent enantioselectivity was found under all conditions studied. The yield was very sensitive to the quality of cell paste. In a rather wide range temperature and aeration did not affect the results of bioreduction.