硫酸奈替米星关键中间体合成工艺研究及有关杂质结构分析

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中图分类号：R978 文献标志码：A

Abstract Objective To investigate the synthesis process of 3，2'，6'-tris（ Nδ -acetyl）sisomicin， the key intermediate of netimicin sulfate，and to analyze its impurity spectrum.MethodsThe key intermediate of netisomicinsulfate，3，2'，6'-tris（N-acetyl）sisomicin，wasobtainedbyusingsisomicinas thestartingmaterial.Then the complexation reaction was carried out with copper acetate，and the amino was propected by acetic anhydride. The reaction mechanism and high-resolution mass spectrometry were used to analyze the relevant impurities of the intermediates，andthe structuresofthe intermediates were inferredthrough thereasonableanalysisof the Known test data.ResultsThe preparation processof the key intermediate of netamicin sulfate，3，2'，6'-tris（N-acetyl）cisomicin （TAS），was studied，andtheimpurities generated during thesynthesisof3，2'，6-tris（N-acetyl）cisamicin （A）from sisomicin were systematically analyzed.ConclusionThe HPLC-QTOF-MS method was established to explore the process andrelated impuritiesof3，2'，6'-tris（N-acetyl）sisomicin，thekey intermediateofnetamicinsulfate，which played an important role in the declaration of consistency evaluation of netimicin sulfate.

Key WordsNetamicin sulfate; Intermediate; Sisomicin; Related impurities; Structural confirmation

硫酸奈替米星属于半合成的氨基糖甙类抗生素，最早于1981年6月首次在法国上市，于1999年10月在中国获批上市。（剩余10079字）