The Research On ω-Transaminase Catalyzed Reductive Amination Of Acetophenones And The Synthesis Of Duloxetine And Dapoxetine

This dissertation consists of two parts:(i)research on ω-transaminase catalyzed reductive amination of acetophenone derivatives;(ii)research on synthesis of duloxetine and dapoxetine.In the first part,we presented a review on the ω-transaminase.Chiral drugs are widely used in medications,some intermediates of which are chiral amines.Thus,the synthesis of chiral amines draws great attention.By introducing several different enzymatic methods to synthesize chiral amines from ketones,we find that the method using ω-transaminase as biotransformation enzyme is an environmental friendly and financially cheap one to asymmetrically synthesize chiral amines.According to this,we tried to use ω-transaminase as catalyst to synthesize a series of chiral amines from acetophenone derivatives,and found that some of substrates have good reactivity.After optimization of the reaction conditions,a typical result is that the conversion of acetophenone to R-1-phenylethan-1-amine catalyzed by ω-transaminase was achieved successively.In the seccond part,we introduced the synthesis of antidepression drugs duloxetine and dapoxetine.1-Fluoronaphthtalene is a key intermediate both of duloxetine and dapoxetine.A diazotization method to synthesis 1-fluoronaphthtalene was improved.The synthetic method for industrial production of 1-fluoronaphthtalene through diazotization were studied intensively and has applied in the industrial production after optimization.Duloxetine was synthesized by the industrialproduction route and we optimized some reaction conditions.In the end,we studied two reduction methods to synthesis dapoxetine,both of them showed good performance with the substrate and then we optimized their reaction conditions.