Synthesis Of Pharmaceutical Intermediate:1-Phenyl Alcohol By Microbial Reduction

With the progress in pharmacology of chiral pharmaceuticals and the strict regulation in the application of new drug in recent years, the research and development of chiral pharmaceuticals has become the new direction internationally. Hence, how to synthesize chiral compounds is the key in commercial production of chiral pharmaceuticals. Many researchers are applying themselves to develop new processes for chiral compound synthesis with high conversion ratio and high stereo-selectivity, in which, biotransformation is attracted interests because of mild reaction condition and high stereo-selectivity.1-phenyl alcohols are important precursors for the synthesis of chiral pharmaceuticals. It has reported that microbes can be used to reduce various carbonyl compounds into chiral alcohols. In this work, the reduction reactions of acetophenone into1-phenyl ethanol catalysed by microbes obtained from the soil will be studied in detail.Using DL-1-phenyl alcohols as the only carbon sources, more than370microorganism strains which can be cultured in selective culture mediums ware obtained. The conversion of DL-1-phenyl alcohol into acetophenone was carried out at the concentration of substrate0.1%(v/v) and the71strains were obtained through the method of2,4-dinitrophenylhydrazine to judge the basic activities of the1-phenyl alcohol dehydrogenase of the strains. Then the conversion was carried out with0.1%(v/v) acetophenone solution as the substrate. Through the detection of the method of2,4-dinitrophenylhydrazine, the method of HPLC C8column as well as the method of chiral column HPLC, one special strain No. XC35-8which can catalyze the conversion of acetophenone in to1-phenyl alcohol effectively and high-stereo-selectively was obtained.Further study of different parameters during the culturing and conversion showed that when taking5g/L glucose as the carbon source and10g/L; tryptone as the nitrogen source; pH7.0; the culturing temperature at30℃; the shaking speed at200r/min, through the whole cell conversion of0.6mL/L acetophenone as the substrate and6%(v/v)2-propanol as the co-substrate to enhance the weak co-enzyme system in the cell, at the pH of7.0and conversion temperature of30℃, after24h, it could be got at the yield of the product S-1-phenyl alcohol of83.4%and the ee value of99.5%.