Exploration And Research Of The Synthesis Of Miglitol By Catalytic Hydrogenation Combined With Biotransformation

According to the internal and external literature, this article discussed the synthesis of miglitol by the combinational methods of microbial transformation and chemical. Now it has been the first choice for the treatment of type II diabetes. it is found that the process include three steps,(1) Glucose and ethanolamines reductive aminate to N-(2-hydroxyethyl) glucamine;(2) The substrate of N-(2-hydroxyethyl) glucamine was successfully converted by G. oxydans into 6-(2-droxyethyl)amino-6-deoxy-a-L-sorbofiuanose, the Key intermediate of miglitol; (3) miglitol was synthetised by catalytic hydrogenation. Study the process of feasibility, isolation and identification of products.RaNi and Pd/C catalyst, the mole ratio ethanolarnine and glucose, pH, temperature and the influence of water on the reaction under low pressure have been studied in the reductive animation synthesis N-(2-hydroxyethyl)glucamine. It was found that the initial hydrogen reaction is in high rate, slow progression in the subsequent reaction, considering catalyst may deactivation. The optimal technological conditions of reductive amination synthesis were as follows: the mole ratio of catalyst and glucose was 10%, the mole ratio ethanolarnine and glucose was1:3, the reaction time was 25h,the reaction temperature was 50℃, the value of pH was 11. The structure of N-(2-hydroxyethyl) glucamine was confirmed by infrared spectroscopy, elements analysis, melting point and MALDI-MS, and the purity was 89%, and the melting range was 131℃～133℃.The substrate of N-(2-hydroxyethyl)glucamine was successfully converted by G. oxydans into 6-(2-droxyethyl)amino-6-deoxy-a-L-sorbofiuanose, the Key intermediate of miglitol .The optimal condition of the bio-catalytical oxidation reaction system was: the suitable inital pH is 5.0, substrate concentration is 20 g/L～80 g/L ,the best temperature is 12℃～15℃, stem cell is 8g/L. Then miglitol was synthetised by catalytic hydrogenation, The optimal condition of the catalytic hydrogenatio reaction system was: high pressure sprayer at pressures below 0.6Mpa, the suitable temperature is 20℃, the amount of catalyst was 10% .The structure of crystal was confirmed by MALDI-MS ,and the melting range was 142℃～147℃.It was the same molecular weight of migliton, by preliminary test, proves that the process of synthesis of miglitol is reasonable.The research which we had studied not only selected of reductive amination catalyst and technological conditions of synthesis but also revealed catalytic oxidation reaction activity and specificity of G. oxydans. It have laied a foundation for prophase work of new drugs of migliton's development.