The Synthesis Of Tigecycline

In this article, progress of research on Tetracycline drugs has been reviewed firstly. Two routes synthesis of Tigecycline was designed, the first process was synthesized using Minocycline as raw material. Nitration of Minocycline with fuming nitric acid gave the intermediate 9-nitrominocycline, then it was reduced by catalytic hydrogenation to give 9-aminominocycline in good yield. Reaction of 9-aminominocycline with the Chloroacetyl Chloride gave the 9-chloroacetaminocycline, the target products tigecycline was prepared by treating 9-chloroacetaminocycline with tert-butylamine.The other process was using Sancycline as raw material. Compound 9-nitrosancycline was synthesized by nitration with Sancycline, then it was reduced to 9-aminosancycline. It was nitration to give 7-nitro-9-aminosancycline, the target product Tigecycline was synthesized by introduction of N-tert-butylglycinamide to the C-9 positions of 7-nitro-9-aminosancycline, then reduction 7-nitro group and methylation the 9-amino group. At present, the compounds of 9-nitrosancycline and 9-aminosancycline were synthesized, the rest of work is going on.The main works in the thesis were finished as follows:1.9-nitrominocycline and 9-nitrosancycline were prepared, and the methods of determination of purity by HPLC were established. The reaction condition such as temperature, time and the ratio of reactants influence on yield of products were studied.2.9-aminominocycline and 9-aminosancycline were prepared by catalytic hydrogenation in autoclave. The two compounds were characterized by LC-MS and 1HNMR. The process was simple and suitable for industrial product.3. Chloroacetyl Chloride with purity of more than 99.0% was prepared by SOCl2 as acylating agent. The method of determined purity of product with GC was established, the compound was characterized by IR.4.9-Chloroacetaminocycline was synthesized, and the structure was characterized by LC-MS and 1HNMR. 5. The target compound tigecycline was synthesized, the best reaction condition was obtained and the influence of such as temperature, reaction time were also discussed. The method of determination the purity by HPLC was established, and the structures of target compound were characterized.