Synthetic method for tildipirosin

Abstract

The invention discloses a synthetic method for tildipirosin. The synthetic method comprises the steps that 20-piperidyl-5-O-mycaminose base-tylosin lactone silicon is subjected to alkylation protection and then has an iodination reaction with iodotrimethylsilane, and 20-piperidyl-23-I-5-O-mycaminose base-tylosin lactone is prepared and then synthesized with piperidine to obtain tildipirosin. The whole process route is simplified, reaction conditions are mild, the reaction is easy to control, the 23-digit allose base does not need long-time hydrolysis, the reaction time is shortened, the overall yield is increased and reaches up to more than 85%, and the product quality completely meets the related standard requirement.

Description

technical field [0001] The invention relates to the technical field of drug synthesis, in particular to a synthesis method of tedirosin. Background technique [0002] Tylosin is the latest macrolide semi-synthetic antibiotic for animals. It uses tylosin as raw material and is transformed through multiple steps. [0003] Animal respiratory diseases have the characteristics of high morbidity and high mortality, which seriously plague the development of the breeding industry. At present, the macrolide drugs used in the treatment and prevention of swine and cattle respiratory diseases in my country are tylosin and tilmicosin, both of which have achieved good results, but with long-term use, there are The problem of drug resistance to different degrees has been solved; at the same time, these two products require multiple administrations to be effective, and the dosage is large and there are many residues. [0004] As a brand-new macrolide antibiotic product, Tedirosin is not on...

AI Technical Summary

Problems solved by technology

The method has many steps, complex operation, low yield and high cost, and is not suitable for industrial production

[0007] 2. US6514946 reported a kind of 20,23-diiodo-5-O-mycaminosyl-tylonolide as raw material, which reacted with piperidine in acetonitrile under reflux, and the reaction solution was subjected to column chromatography to obtain Taidi Luo Xin's method, the method 20,23-diiodo-5-O-mycaminosyl-tylonolide is not easy to get, column chromatography is not conducive to industrial promotion

[0008] 3. CN201410108841 reported a method of using tylosin tartrate as raw material, through ammoniation, hydrolysis with high-concentration strong acid, oxidation with sodium hypochlorite, and ammoniation with piperidine to prepare tedirosin. The method is to make the 23-position hydroxyl The reaction generates aldehyde groups. This reaction is a selective oxidation reaction. It is not easy for people to strictly control the reaction process at the stage of generating aldehyde groups, and aldehydes are generally unstable, so the reaction process is difficult to accurately control.

The reaction conditions are harsh, the process route is difficult to control, and the yield is not high

[0009] 4. CN102863487 reported a method of using tylosin tartrate as raw material, hydrolysis with high-concentration strong acid, iodization, and finally ammoniation with piperidine to prepare tedirosin. The risk of generation, affecting the yield and purity of the product

[0010] The above methods all need to carry out a long-term hydrolysis reaction on the allosyl group at the 23-position under the action of high-concentration strong acid, which will cause certain damage to the structure of the raw material, more side reactions, and a lower reaction yield.

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