| In this thesis, the main work is chemo-enzymatic deracemization of chiral aryl diols and preliminary study on biocatalytic synthesis of (S)-N-Boc-3-hydroxypiperidine.First, racemic aryl diols were prepared by using aryl ethylene as the raw material.Then the growth and enzyme activity of three yeast cells were investigated, and Pichia etchellsh SIT2014 was chosen as the biological catalyst of chemo-enzymatic reaction. Pichia etchellsii SIT2014 could reduce 2-hydroxy aryl ketone to chiral aryl diols with high yield and high optical purity (yield=100%, ee>99%) after fermenting 24 h in conditions of 30℃,180 rpm.Third the chemical reaction was carried out in a mild reaction system which included H2O, β-cyclodextrin (β-CD) and N-Bromosuccinimide (NBS). The effects of temperature, time, the amount of NBS and β-CD were investigated, respectively. Finally the yield of oxidation reaction reached almost 100% using the substrate/NBS/β-CDratio of 1:2.3:lat 60℃ after 9 h.To realize chemo-enzymatic reaction, it’s important to solve the problem of bio-compatibility. All of the substances appearing in the oxidation reaction such as the amount of NBS or β-CD which may have effect on next biological reaction had been studied, respectively. Finally S-aromatic vicinal diols were obtained in high yield and optical purity. The ee value of (S)-1-phenyl-1,2-ethanediol, (S)-1-(4-bromopheny)-1,2-ethanediol, (S)-1-(4-chlorophenyl)-1,2-ethanediol and (S)-1-(3-chlorophenyl)-1,2-ethanediol was 98.8%, 97.3%,98.1% and 99.4%, respectively, and the analytical yield of them were all up to 99%.Finally, (S)-N-Boc-3-hydroxypiperidine, which is the intermediate of anti-tumor drugs, was synthesized by asymmetric reduction using Pichia etchellsii SIT2014 as biocatalyst. The effects of pH, substrate concentration, reaction solvent were studied in the enzymatic reaction. By controlling a pH of 7.0 and adding 5% glucose to phosphate buffer solution, (5)-N-Boc-3-hydroxypiperidine could be obtained with>99% ee and 85.4% yield. |
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