Asymmeric Synthesis Of 1-Phenyl-1,2-Ethanediol Derivatives Catalyzed By Baker's Yeast

1-Phenyl-1,2-ethanediol derivatives are optically active compounds with a hydroxyl on the chiral carbon, which are important in the synthesis of pharmaceuticals, pesticides and materials. Carbonyl compounds can be asymmetric reduced in many ways, but the biocatalysis method is the effective one for the advantages of green and high efficiency. Baker's yeast is widely used due to its cheap and good reduction properties.Fiveα-hydroxyacetophenone derivatives were synthesized with microwave irradiation. The effecting factors including reaction time, pressure and substrate concentration were studied. The optimal conditions were obtained, which wreα-bromoacetophenone derivatives quality content of 12 g / L, microwave irradiation time of 25 min, the reaction pressure of 0.30 MPa. It was found that the microwave played an important role in promoting the reaction. Compared with traditional synthesis, microwave assisted synthesis reaction gained a good yield in a short time. At the same time, water was used as green and economic environment reagents and solvents, which met the requirements of green chemistry. Therefore, the acquiredα-hydroxyacetophenone derivatives were used as the substrates for catalytic asymmetric synthesis in preparing of 1-phenyl-1,2-ethanediol derivatives by baker's yeast.A simple chemical reduction method was chosen for the fiveα-hydroxyacetophenone derivatives reduction using sodium borohydride as reducing agent. The five racemic products were obtained and purified by column chromatography, and also analyzed by HPLC with capillary column, respectively. And the corresponding retention times of S-configuration and R-configuration product were obtained, which provides a reference for the next asymmetric reduction catalyzed by baker's yeast.In this paper, the asymmetric reduction of fiveα-hydroxyacetophenone derivatives was studied firstly using a mild and environmentally friendly water solution as medium and baker's yeast as biological catalyst. The effecting factors, including reaction time, pressure, pH and substrate concentration, were investigated and optimized by single factor experiment. Conversion of substrate and enantiomeric excess value of R-1-phenyl-1,2-ethanediol derivatives were used as evaluation index. Experimental results showed that when the substrate concentration was 15 mmol/L, the amount of baker's yeast was of 70g/L, reaction time was 12 h and reaction temperature was 32℃, the conversion of other 4α-hydroxyacetophenone derivatives could reach more than 97.2% and e.e. values over 96.0% except 2-hydroxy-1-(4-methoxylphenyl)-ethanone, which its conversion rate was 73.4% and e.e. value was 94.2%. We found that the transformation of substrates which substrated with chlorine on the benene ring were higher than methyl and methoxy substituted substrates. We also found that non-aqueous buffer system were better than the buffer system, while the absence of additives in the water phase, baker's yeast cells began to decline after 46 h, the reaction time was less than 46 h.