Study On The Synthesis Route Of Gamithromycin

Gamithromycin is a semi-synthetic macrolide veterinary medicinal product. Gamithromycin hasboth bacteriostatic and bactericidal action, mediated through the disruption of bacterial protein synthesis.It is an azalide antibiotic with only one stable polymorph form identified. The broad spectrumantimicrobial activity of gamithromycin includes Mannheimia haemolytica, Pasteurella multocida andHistophilus somni, the bacterial pathogens most commonly associated with Bovine RespiratoryDisease（BRD）.Gamithromycin is derived from the starting material erythromycin a thiocyanate.9（E）-9-deoxo-9-hydroxyiminoerythromycin A is made by the reaction of oxide with the the startingmaterial erythromycin A.9（Z）-9-deoxo-9-hydroxyiminoerythromycin A is generated by the alkalinecatalyst of9（E）-9-deoxo-9-hydroxyiminoerythromycin A. Then the reactions of Beckmannrearrangement generate the erythromycin imines ether mixture. The synthesis of9-deoxo-8α-aza-8α-homoerythromycin A is by the process of reduction by sodium borohydridereagent.Gamithromycin is synthesized by the Reductive amination.The paper also optimizes the process of gamithromycin and tests the intermediates. Use thesodium cyanoborohydride in the reductive amination reaction of Gamithromycin first time and get agood yield. Gamithromycin is macrolides antibiotics and9（E）-9-deoxo-9-hydroxyiminoerythromycin Aand9（Z）-9-deoxo-9-hydroxyiminoerythromycin have the same reaction. So there are lots of manyisomers. The final product is got from the column chromatography many times. We studied syntheticroutes of gamithromycin and successfully got the gamithromycin with lower material cost, high yieldand simplicity of operation. All the intermediates and gamithromycin were confirmed by IR, meltingpoint, MS,¹H NMR and¹³C NMR.The innovative point of this paper was that reduction amination reaction used sodiumcyanborohydride to get Gamithromycin.The broth macrodilution antifungal susceptibility test was used to detect bacteriostasisi activityfor different products. And minimal inhibitory concentration is the reflection for different product’sbacteriostasis activity. The antibacterial activity of compounds is evaluated in vitro, and results indicatethat gamithromycin showed better antibacterial activity than azithromycin against tested Gram-positivemicroorganisms. Against Gram-negative bacteria activity is very weak.