电喷雾电离质谱监测合成帕拉米韦的反应副产物

Identification of products formed in side reaction in peramivir synthesis with electrospray ionization-mass spectrometry

目的:利用电喷雾电离串联质谱监测合成帕拉米韦的反应副产物,推测副产物化学结构及相对含量,为快速改进帕拉米韦的合成工艺提供依据。方法:以文斯内酰胺为初始原料,经催化开环、氨基保护、开环加成等多步反应合成帕拉米韦三氟乙酸盐。质谱条件:质谱采用电喷雾正离子模式(ESI+),质量扫描范围为m/z50～800。反应终溶液经甲醇稀释直接测定,并测定一级质谱中主要离子的二级质谱。结果:反应终溶液的ESI-MS谱中,主要为m/z329.0及313.1的2个峰,分别是目标化合物帕拉米韦及其脱氧反应副产物的[M+H]+峰。脱氧副产物的含量约为帕拉米韦的80%。结论:利用电喷雾电离串联质谱监测帕拉米韦合成反应,可快速推测反应副产物化学结构及其相对含量,为改进其合成工艺提供重要依据。

Abstract Objective： To detect side reaction products formed in peramivir synthesis with electrospray ionization-tandem mass spectrometry （ESI-MS/MS）, and infer chemical structures and relative contents of side reaction products. Methods： Peramivir was synthesized with 2-azabicyclo[2,2,1]- hept-5-en-3-one as starting materials and through multi-steps reactions including amide hydrolysis, amino group protection and addition reaction.. ES1 was applied and operated in positive ion mode. The scanning range was m/z 50~800. The product solution were diluted with methanol and analyzed directly by ESI/MS. Product ions of main ions in primary mass spectrum were obtained by CID. Results： Main ions with m/z 329.0 and m/z 313.1 in primary mass spectrum of product solution were identified as [M ＋ H＋] ions of peramivir and deoxy-peramivir. Conclusion： ESI-MS/MS was a powerful instrument to detect side reaction products in peramivir synthesis, and chemical structures and relative contents of side reaction products could be inferred.