克拉霉素A-(<i<E</i<)9-<em<O</em<-甲基肟的合成与分离
Synthesis and Separation of the Clarithromycin A<i<E</i<-9-<em<O</em<-Methyl Oxime
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摘要: 为了控制和跟踪克拉霉素合成工艺,制备了克拉霉素A(<em<E</em<)-9-<em<O</em<-甲基肟. 以克拉霉素肟为原料,通过硅烷化、甲基化和脱保护三步反应合成了克拉霉素A(<em<E</em<)-9-<em<O</em<-甲基肟,并进行了HPLC分析和表征(<sup<1</sup<H NMR和<sup<13</sup<C NMR). 实验结果表明,反应的催化剂、溶剂和pH值会对此化合物的合成产生很大影响. HPLC分析条件:流动相为乙腈∶KH<sub<2</sub<PO<sub<4</sub<(0.033 mol/mL)=45∶55(pH=4.0),检测波长210 nm,柱温为30 ℃,流速为1.0 mL/min. 此化合物的合成有利于用HPLC方法对反应进程进行有效跟踪与质量监控.Abstract: To control the commercial production of clarithromycin, clarithromycin A(<em<E</em<)9-<em<O</em<-methyl oxime was synthesized using clarithromycin A oxime as the raw material by three steps:protection of 2′-OH and 4″-OH with TMS, methylation and de-protection of TMS. The structure was identified by <sup<1</sup<H NMR, <sup<13</sup<C NMR and HPLC analysis was conducted. Experimental results show that the reactions are greatly affected by catalyst, solvent and pH value. The parameters of HPLC are as follows. The mobile phase is ACN/KH<sub<2</sub<PO<sub<4</sub< aqueous solution (<em<V/V</em<=45/55), wavelength is 210 nm, temperature is 30 ℃ and the velocity of flow is 1.0 mL/min. This synthesized compound is of benefit to control the commercial production of clarithromycin.
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