Studies On Synthesis Technology Of Tulathromycin

Tulathromycin is a new semi-synthetic marolide only used as veterinary drug for treatment of respiratory diseases especially for SRD and BRD caused by Actinobacillus pleuropneuminiae, pasteurella, mycoplasma, etc. It not only has long half-time and lower toxicity and side-effect but also resolves the problem on drug-resistant of tylosin and tilmicosin. But the large-scale production is restricted because of the complicated synthetic steps and exorbitant cost. So researching for an efficient and low cost synthetic route gets more and more attention of scientists. In this thesis we find a novel synthesis process of Tulathromycin based on the previous studies.9a-NH and2’-OH protected9a-NH azithromycin was synthesized by oximation reaction, Beckmann rearrangement and reduction reaction. And then this important intermediate was used for synthesis of tulathromycin through Swern oxidation reaction, Corey-Chaykovsky epoxidation, deprotection and ring-opening reaction. What else was worth mentioning wass the protecting group used was acetyl group and "one pot" reaction of deprotection and ring-opening reaction in n-propylamine was realized.Compared with the route reported by Pfizer, the cheaper protecting group acetyl was used to instead of Cbz and the reaction process was shortened to four steps.The pilot-scale experiments were achieved and we found:(1) compared to small-sized experiments, the yields were stable in every step and a little improved in the third and forth steps.(2) mild reaction condition, simple steps without specific equipment and serious pollution made it ideal for industrial production.