目的 設(shè)計并合成了溴甲納曲酮在光照、氧化及堿性條件下的3個降解產(chǎn)物。方法 以鹽酸納曲酮為起始原料分別經(jīng)過500 W紫外燈照射、過氧叔丁醇的三羥甲基氨基甲烷溶液的氧化,氫氧化鈉的霍夫曼降解反應(yīng)得到3個結(jié)構(gòu)不同的降解產(chǎn)物。結(jié)果 合成了目標(biāo)化合物,并利用質(zhì)譜和核磁數(shù)據(jù)確證了結(jié)構(gòu);目標(biāo)化合物1～3的質(zhì)量分?jǐn)?shù)分別為99.77%、94.18%、99.51%,收率分別為35.5%、40.0%、25.1%。結(jié)論 3個降解雜質(zhì)的合成與分離為溴甲納曲酮的雜質(zhì)研究奠定了物質(zhì)基礎(chǔ)。

Objective To design and synthesize three degradation products of methylnaltrexone bromide under light, oxidation, and alkaline conditions. Methods Methylnaltrexone bromide was used as raw material to synthesize the three different structure compounds by lighting under 500 W ultraviolet light, oxidation with t-butylhydroperoxide in TRIS solution, Hoffmann degradation with sodium hydroxide. Results The target compounds were synthesized and characterized by MS and NMR data. And the purity detected were 99.77%, 94.18%, and 99.51%, respectively. The yields of three target compounds were 35.5%, 40.0%, and 25.1%. Conclusion The synthesis and separation of three degraded products of methylnaltrexone bromide lay the material base for the study of impurities in methylnaltrexone bromide.