脱氢环氧甲基醌霉素的合成工艺改进研究

Improvement of method for synthesis of dehydroxymethylepoxyquinomicin

目的对脱氢环氧甲基醌霉素(DHMEQ)的合成工艺进行改进研究。方法以阿司匹林和2,5-二甲氧基苯胺为起始原料,经缩合、碘苯二乙酯氧化、过氧化氢环氧化、酸催化脱缩酮保护、Na BH4还原成目标化合物,关键的环氧化步骤采用HPLC监控并通过调整反应条件进行工艺优化。结果剔除了柱色谱步骤,优化后制得的目标化合物质量分数为99.4%,工艺总收率为30.0%。结论 DHMEQ的合成工艺改进后操作简便,产品质量可控,适合工业化生产。

Objective To study the improved method for synthesis of dehydroxymethylepoxyquinomicin （DHMEQ）.Methods Aspirin and 2,5-dimethoxyaniline were used as starting materials to synthesize the target compound by condensation, oxidation with （diacetoxyiodo）benzene, epoxidation with hydrogen peroxide, deketalization by acid catalysis, and NaBH4 reduction. The key process was the epoxidation reaction that was monitored by HPLC, and reaction condition was adjusted to optimize the synthetic process. Results The process of column chromatography could be eliminated. After optimization, the purity of target compound was 99.4%, and the total recovery of the synthetic route was 30.0%.Conclusion After optimization, the synthetic process of DHMEQ has the advantage of simple operation, and the product quality can be controlled. Therefore, the improved method for synthesis of DHMEQ is suitable for industrial production of drugs.