Tigecycline synthesis research

Objective:Tigecycline is a new generation of tetracycline antibiotics after the development of doxycycline,minocycline and metacycline. It is the first aminoacetamide tetracycline antibiotics which was allowed in the market.Combined with the research progress of Tigecycline in domestic and overseas, our research mainly focuses on the synthetic of Tigecycline and its process optimization. In order to get a mature technology of high yield、high purity、controllable quality, for tigecycline of production to provide technical supportMethods:When studying the synthetic route of tigecycline,Overall consideration factors such as cost, equipment, production rate, We confirmed that the synthetic route of tigecycline. The structure of target product was confirmed by nuclear magnetic resonance hydrogen spectrum and the carbon spectrum. We researched every step of the technology process in the synthetic route respectivily. Taking time, temperature, PH, the kind and dosage of catalyst and solvent, crystallization agent and some other condition as observation factors, we studied the purity and productivity of the product obtained under different conditions.The condition with high purity and productivity is the optimal reaction condition in every step(which is tested by the HPLC-High Performance Liquid Chromatography). So we confirmed the optimal technology process to synthesis tigecycline.Results:We confirmed that tigecycline is synthetized as the following way:the target compound was obtained with minocycline hydrochloride as the starting material, through the five-steps reaction which including nitration, hydrogenation reduction, salt conversion, amidation and refinement, we obtained the target compound Tigecycline. Under the optimal process conditions, the quality is easy to be controlled. Every step of the reaction, the most productive rate can reach91.8%,72.5%,71.8%,72.0%,70.8%, and the Tigecyclineis total yield can reach24.03%, the purity is99.7%.Conclution:The production process in this research, it is easy to get raw materials steadily、besides, Mild reaction conditions、easy to operation、have a better reproducibility and the quality is easy to be controlled,and facilitate industrial production.