Asymmetric reduction of 4-methoxy acetophenone by lactobacillus senmaizuke biocatalyzer using box-behnken design-based optimization strategy

Biocatalysts are increasingly used in the production of important chemicals as they are more selective, environmentally friendly and safer than traditional chemical catalysts. Enantiopure chiral secondary alcohols are important as precursors for the synthesis of drug, biological active molecules and other chemicals. The functional group of chiral secondary alcohols can be easily transformed into other functional group without racemazation. Enantiomerically pure (R) and (S)-1-(4-methoxyphenyl)ethanol is an important molecule for the production of various drug intermediates such as loratadine, antihistamines and diphenhydramine hydrochloride. In this thesis, this key molecule was synthesized from 4-methoxyacetophenone using Lactobacillus senmaizuke as a biocatalyst. The reaction conditions, such as pH, incubation period, temperature and agitation speed, were optimized using Box-Behnken experimental design-based optimization strategy. The predicted bioreduction conditions for the reduction of 4-methoxyacetophenone to (S)-1-(4-methoxyphenyl) ethanol with whole-cell Lactobacillus senmaizukei were found to be temperature of 29ºC, pH of 5.8, agitation level of 155 rpm and incubation period of 50 h. (S)-1-(4-methoxyphenyl) ethanol was produced using Lactobacillus senmaizuke in >99% conversion, >99% enantiomeric excess and 96% yield in this optimum bioreduction conditions. The efficiency of the bioreduction of 4-methoxyacetophenone was importantly affected by the quadratic and linear effects of culture parameters. These results are crucial to demonstrate the role of culture optimization parameters for catalytic bioreduction reactions and the effectiveness of the Box-Behnken method to optimize these parameters.