Improving Process Of Synthesis Of Tulathromycin And Research Of Asymmetic Beckmann Rearrnangement Reaction

Trulathromycin is a new-style macrolides antibiotic for animals which is also know as Draxxin as a kind of durg. Draxxin is a kind of the latest macrolides antibiotic for animals which was exploited by Phizer Animal Health Company and hit the European and American market since2004, and it is mainly used for the prevention and cure for pig and cattle's respiratory system infectious disease caused by sensitive bacteria and cattle's infectious keratoconjunctivitis caused by Moraxella bovis. Trulathromycin is with excellent pharmacokinetic characteristic. It can be quickly absorbed and reach Cmax quickly. It is also with high bioavailability and can reach very high organization concentration in animals'lungs. Moreover it is with long efficacy so can eliminate half-time for a long time. It can provide a full-course therapy after a single muscle injection or subcutaneous drug delivery. At present, the injecta of Trulathromycin has come into china market. Because of its obvious therapeutic effect it has a wide application prospect in veterinary clinical direction.Trulathromycin is a new-style macrolides antibiotic for animals. This study is intended to explore improved synthetic process route for trulathromycin which using azithromycin-A as the raw material. First, protective azithromycin-A (11) was prepared by reaction of azithromycin-A and Cbl-Cl, in this reacting the second hydroxide radical of azithromycin-A was protected in the presence of Cbl-Cl. Next, Cbz-protected ketone (Ⅲ) was prepared when the protective azithromycin-A (Ⅱ) was oxidized in the forth hydroxide by using Albright-Goldman method. Then protective alkene (Ⅳ) was prepared in the reacting of Witting-Horner when ketone group conveted alkenyl. After, Cbz-protected epoxy compound(Ⅵ) was prepared with protective alkene (Ⅳ) was oxidized in the presence of hydrogen peroxide. After, deprotected epoxy compound was prepared with Cbz-protected epoxy compound(Ⅵ) deprotected by using Pd/C as the catalyst. Crude product of rrulathromycin was prepared by reaction of deprotected epoxy compound and propylamine. Finally, the crude product was purified by phosphate and then analized obtained rrulathromycin(Ⅶ) in42.0%yield with98.00%purity determined by HPLC (High Performance Liquid Chromatography). This study proposed new improved combining route, in the route, the reactions needn't be at a low temperature compared with previous method. It can be effectively used in industrial production.This study is intended to search asymmetric Beckmann rearrangement. Beckmann rearrangement plays an important roles in organic synthesis which can prepare diamide compounds. In accordance with literature, the study assume four different asymmetrical Beckmann rearrangement reaction apply different catalysis system to rearrangements of different para-position perssad cyclohexanone in order to observe selectivities of rearrangements. The study provides foundation in a certain extent for the development of asymmetrical Beckmann rearrangement in the future.