Dissertation > Medicine, health > Pharmacy > Drug basic science > Medicinal Chemistry

Study on the Asymmetric Bioredution of 3-Chloropropiophenone with Highly Active Bread Yeast Cells and Its Optimum Biotransformation Condition

Author TongLingZuo
Tutor LuoZhi
School Huazhong University of Science and Technology
Course Medicinal Chemistry
Keywords asymmetric bioreduction bread yeast cells 3-Chloropropiophenone orthogonal experiment visual analysis variance analysis
CLC R914
Type Master's thesis
Year 2010
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Aim In anaerobic circumstance, asymmetric bioredution with highly active bread yeast cells for 3-Chloropropiophenone was studied, and produced a chiral alcohol which was (S)-(-)-3-chloro-1-phenyl-propanol.Bioreduction condition and the method of separation and purification were improved. In guarantee of high optical purity, effects of temperature、pH value、substrate concentration、reaction time、bread yeast concentration、the kinds of co-substrate and D-glucose concentration were evaluated by orthogonal experiments and visual analysis to get optimum biotransformation condition and high yield. The predominant factors can be obtained by variance analysis and SPSS software.Method In a stirring device of anaerobic circumstance, the asymmetric bioreduction started from 3-Chloropropiophenone and highly active bread yeast cells. The ethanol was added under stirring as co-substrate. After the high temperature activation and suitable bioreduction time, proper celite was added in the reaction mixture. (S)-(-)-3-chloro-1-phenyl-propanol was extracted from reaction solution with excellent enantioselectivity. Its structure was verified by IR、1H-NMR、13C-NMR.The melting point and specific rotation were assessed by melting point apparatus and polarimeter. In order to enhance bioreduction yield, while the product field was designed as analysis standard optimum parameters were investigated by orthogonal experiments. In guarantee of high optical purity, perfect reaction conditions were analyzed by visual analysis, with the help of SPSS software, the predominant factor was studied by variance analysis.Result The (S)-(-)-3-Chloro-1-phenyl-1-propanol was gained by the first part of asymmetric bioreduction. The reaction field was 60%. The IR、1H-NMR and 13C-NMR were the same to the cited parameters of literature. The specificrotation was -23.8o. The enantiomeric excess value reached 100%. The melting point was from 58℃to 60℃. The optimum biotransformation condition was 23℃、6.5(pH value)、63 h、4 g/L as substrate concentration、200g/L as yeast concentration、120g/L as D-glucose concentration、40mL enthanol a co-substrate(in the 1L buffer solution). The high yield of the optimum biotransformation condition which was at the top of orthogonal experiments was 72%, Its structure was verified by IR、1H-NMR。The predominant factors were substrate and co-substrate when they were statistically significant (P<0.05). 8 factors had no interaction with each other, and were easy to dominate.Conclusion Compared with the cited literature, the method of extraction and purification and bioreduction condition were improved. With the investigation of orthogonal experiments, the overall yield was increased. The optimum of the transformation of 3-Chloropropiophenone was acquired. The predominant factors were achieved. All of those will satisfy the requirement of industry.

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