Study On The Process For Preparation Of Key Intermediates Of Dibekacin

Dibekacin (3',4-dideoxykanamycin B) is a new semisynthetic aminoglycoside antibiotics developed in Japan and one which has found wide clinical acceptance in that country..Dibekacin is a new type of low toxicity antimicrobial and broad-spectrum drugs with antimicrobial mechanism and.unique chemical structure It has a little cross-resistance with other antibiotics or antimicrobial agents.The novel process for synthesis of the key intermediate of Dibekacin was studied in this paper.Three synthetic routes were reviewed on the basis of relevant references.The optimum process parameters were discussed..kanamycin B is reacted with tosyl chloride to protect the five amino groups of kanamycin B in aqueous dioxane in the presence of Na2CO3, and then the pair of 4"and 6"-hydroxyl groups are selectively protected into ketal by reacting with cyclohexanon dimethylketal at 60℃in DMF. The compound 3 can be converted into the 3',4'-di-O-benzylsulfonyl-penta-N-tosyl-4",6"-O-cyclohexylidene kanamycin B (5)and 3',4',2"-tri-O-benzylsulfonyl-penta-N-tosyl-4",6"-O-cyclohexylidene kanamy-cin B (4) by the reaction with benzylsulfonyl chloride in pyride and dichloromethane at-5℃.The compounds 4 and 5 are treated with NaI in DMF at 120℃,to produce the 3',4'-unsaturated derivatives which are subjeced to catalytic hydrogenation after removmed the protecting groups to yield 3',4'-dideoxy-3'-enokanamycin B(10).The route foe synthesis of dibekacin is free from drawbacks of the known method, which is operaable with a reduced reaction steps and have an imprroved key interme-diates'yeild..It is useful to set up a foundation of industry production of Dibekacin.. In this paper, the strueture of intermediates were confirmed by 1H-NMR,13C-NMR.