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Duloxetine hydrochloride, the chemical name (S)-N-methyl -3 - (1 - naphthalenyloxy) -3 - (2 - thien-yl) -1 - propylamine hydrochloride, commodity name Cymbalta, 5 - 5 - serotonin and norepinephrine reuptake of serotonin and norepinephrine reuptake inhibitor (SNRI), can effectively inhibit. Clinically for the treatment of severe depression, female stress urinary incontinence and diabetic peripheral neuropathic pain. Synthesis of duloxetine reported a variety of methods, the paper duloxetine Synthesis comprehensive analysis to determine the to 2 - acetyithiophene as the starting raw materials, through the six-step reaction synthesis of duloxetine hydrochloride , relates to a Mannich reaction, reduction with sodium borohydride, the S-() mandelic acid split into ether, demethylation, salt formation reaction step. Each specific step is performed by the reaction raw material molar ratio, the amount of solvent, reaction temperature, reaction time and other alternative methods specific analytical operations to increase the yield of the synthesis of, the main purpose of the present study is the synthesis of duloxetine hydrochloride optimized process route improvement, in order to improve the yield and reduce the economic cost. Baker's yeast (Baker's yeast) is a widely exploited cheap microbial one capable of catalyzing the asymmetric reduction reaction of the majority of the carbonyl ester, yeast rich oxidoreductase catalytic various carbonyl compounds, asymmetric reduction, have a high degree of stereoselectivity, and just add a cheap source of carbon in the catalytic reaction process can make the cell regeneration catalytic asymmetric reduction required expensive kinds of coenzyme all the enzymes and coenzyme are relatively mild the reaction environment is not easy inactivation, using catalytic reaction was continued. Baker's yeast is cheap, safe operation, easy to use, harmless to the human body. This paper attempts to use baker's yeast asymmetric restore duloxetine intermediates, instead of the sodium borohydride reduction of the original route, S-() mandelic acid split step, saving the cost of the process. Simultaneously compare the various properties of the organic solvent, and found that the change of the organic solvent greater impact, the selectivity of the baker's yeast to determine the water as the reaction solvent. The inhibitor selection discussed in detail the asymmetric reduction reaction of the organic solvent, the selection and ratio of the energy donor, substrate concentration, yeast amount, the reaction system pH, reaction temperature, reaction time and other factors, considering various indicators , improve the yield and conversion rate. By various methods of synthesis process of research and improvement, the overall yield of the final product was 18.6%. Baker's yeast in the biocatalytic asymmetric reduction steps, also no reported both at home and abroad.
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