纳洛酮的合成工艺改进

Improvement on the synthetic process of Naloxone

目的用价廉试剂完成去氧甲基反应,改进纳洛酮的合成工艺。方法在以蒂巴因为原料,经氧化、氢化、酰化、氰化、去氧甲基、水解、N-烯丙基化得到纳洛酮的合成路线中,分别采用甲磺酸/DL-甲硫氨酸和氢溴酸代替三溴化硼进行去氧甲基化和后续水解反应。结果优化了纳洛酮的合成工艺,甲磺酸/DL-甲硫氨酸法试剂价格低廉,可降低生产成本;而氢溴酸法不但试剂价格更低,还可将去氧甲基化和水解合并为一步反应,使新工艺的总收率提高到59.90%,产品质量符合中国药典。结论采用20%的氢溴酸作为去氧甲基化试剂的新工艺,收率高、成本低、操作简便,适合规模生产。

Purpose To seek new method for O-demethylation and improve the synthetic process of Naloxone.Methods Naloxone was synthesized starting from oxidation of thebaine,followed by hydrogenation,acylation,cyanidation,O-demethylation,hydrolyzation and N-allylation.The alternative method of O-demethylation,methane sulfonic acid/DL-methionine and hydrobromic acid were investigated.Results The synthesis condition was improved.The method of methane sulfonic acid/DL-methionine was found an ideal substitute of BBr3 for l...