3-羟基-6-O-甲基红霉素A9-肟的合成

从克拉霉素的前体 6 O 甲基 2′, 4″ 二 (三甲基硅 ) 红霉素A 9 ( 1 异丙氧基环己基 )肟出发,在φ(C2H5OH) =50%的乙醇水溶液中加入甲酸,加热回流 2h脱去保护得到 6 O 甲基红霉素A9 肟,将它悬浮于水中,在w(HCl) =1%的盐酸水溶液作用下水解去除 3 克拉定糖得到目标化合物 3 羟基 6 O 甲基红霉素A9 肟,它是合成对耐药菌有优良活性的第三代红霉素酮内酯和酰内酯的重要中间体, 收率为 73 3%。为了简化反应步骤,试探了在脱保护一步不分离产物而在w(C2H5OH) =95%的乙醇和w(HCl) =2%的盐酸水溶液反应体系中直接水解脱糖的方法,得到了目标化合物,总收率为 69 0%。通过1HNMR、13CNMR和MR确定了目标化合物的结构。

Synthesis of 3-Hydroxy-6-O-methylerythromycin A 9-Oxime

Deprotection of 6-O-methyl-2′,4″-bis(trimethylsilyl)-erythromycin A 9-(1-isopropoxycyclohexyl)oxime,a precursor of clarithromycin,was conducted in φ(C_2H_5OH)=50% aqueous ethanol solution with dropping formic acid under reflux for 2 h to yield 6-O-methylerythromycin A 9-oxime,which was further hydrolyzed in diluted hydrochloric acid 〔w(HCl)=1%〕 to remove 3-cladinosyl group.As a result,the desired product 3- hydroxy-6-O-methylerythromycin A 9-oxime was formed in 73.3% yield.It is an important intermediate for the synthesis of the third generation of erythromycin,i.e.ketolides and acylides with excellent activity against drug-resistant pathogens.In order to simplify the synthesis,the two steps were combined and the reaction was carried out in a mixture of ethanol 〔w(C_2H_5OH)=95%〕 and hydrochloric acid 〔w(HCl)=2%〕 without separation of 6-O-methylerythromycin A 9-oxime.The final product was obtained in 69.0% over-all yield.The structure of the target compounds were identified by ~1HNMR,~(13)CNMR and MS.