The Study Of The Synthesis Of Azithromycin

Azithromycin is a broad spectrum drug that is synthesized from erythromycin. It is the first macrolide antibiotic, and it is the first azalide. Azithromycin has become one of the most popular drugs of the world. It has been extensively used in the treatment of respiratory tract and soft tissue infections.In this thesis, large numbers of related litertures were summarized, the antibacterial activity, structure-activity relationship of erythromycin and its derivatives, the direction of the chemical medification were reviewed. The process for the preparation of azithromycin was also detailed analyzed.Following the reported methodlogies, we studied the synthetic route of azithromycin and successfully prepared the azithromycin with lower material cost, simplicity of operation and higher yield. The route includes four parts: the oximation of erythromycin A, the oxime's Beckmann rearrengment, reduction of the iminoether and Eschweiler W-Clarke H T methylation to obtain Azithromycin. The synthetic route is as following:The oximation reaction synthem was a good acid-base buffer which greatly prevent the decompose of erythromycin, increase the yield and purity of the erythromycin oxime. In the reaction of Beckmann Rearrangement, the reaction temperature was increased to room temperature, the reaction generated three isomers and obtain one product in the process of the reduction reaction, the yield was higher than litertures. Additional, in this thesis, we used "one scoop" process to obtain erythromycin iminoether which was not reported before. Methylation was directly followed by reduction without isolation and purification of the intermediate, the result of the experiment was satisfactory. We used the cheap solvent actone and water as the solvent of the recrystallization of the crude azithromycin. In this thesis, we also studied the synthetic route of erythromycin oxime by using erythromycin thiocyanate whose price is less than erythromycin, which created well base for the industrialization.All the intermediates and products were confirmed by ESI-MS, IR, H-NMR and C-NMR. In particular, the physical form of the finished azithromycin product was proved to be steady dihydrate through the TGA analysis that make it useful in preparing pharmaceutical preparations.