Study On The Optimization Of Synthesis Tigecycline By Bingshun Liu

Tigecycline is a clinical intravenous administration of glycyl doxycycline antibiotics, which is deleloped first in the United states by the Wyeth company. It is named (4S,4aS,5aR,12aS)-4,7-Bis(dimethylamino)-9-[(tert-butylamino)acetamido]-3,10,12,12a-te trahydroxy-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracen-2-carboxamide. Tigecycline is approved by FDA in June2005for the complicated intra-abdominal infections caused by Gram-negative or positive pathogens, anaerobic organisms and methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA) and complicated skin and soft tissue infectionsIn this thesis, through the analysis of the literature synthesis method for the tigecycline, ultimately we selected minocycline as the raw materials. After nitration with potassium nitrate and concentrated sulfuric acid, reduction reaction, amide with bromine acetyl bromide reaction, and with tert-butylamine reaction, we obtained the product finally. However, because of the low yield in the last step substitution reaction with the t-butylamine, prevented our company to expand the scale of production, and affecting the cost of this goods. Therefore, we preferred feed ratio and optimizing of reaction time and temperature and other methods to optimize the process.All products were characterized by modern analytical methods including UV, IR and1HNMR, and their structures are assured.In conclusion, through the synthetic route of tigecycline we designed, we simplified the production process, reduced production costs, furthermore, we can obtain high purity and high yield intermediates, and provide a theoretical and experimental basis for tigecyciline industrial production...