稳定同位素标记特布他林-D_(9)的合成研究

Synthesis of Stable Isotope Labeled Terbutaline-D_(9)

稳定同位素标记的特布他林-D_(9)是以叔丁胺-D_(9)为标记前体,以3,5-二羟基苯乙酮为起始原料进行合成。3,5-二羟基苯乙酮经过苄基保护、溴化、胺化、还原、脱苄基等5步反应制备得到特布他林-D_(9)。通过对反应条件的优化,得到稳定的较优合成工艺路线。以投入的叔丁胺-D_(9)的物质的量计算,特布他林-D_(9)产率为23.3%。目标产物结构经核磁共振波谱、高效液相色谱和高分辨质谱等表征确认。特布他林-D_(9)的化学纯度98.5%,同位素丰度98.4 atom%D,可作为同位素内标用于肉类食品中特布他林残留检测。

The stable isotope labeled terbutaline-D_(9)was synthesized with 3,5-dihydroxyacetophenone as starting material and using t-butylamine-D_(9)as a stable isotope starting labeling raw material.It was prepared by benzyl protection,bromination,amination,reduction and debenzyreaction from 3,5-dihydroxyacetophenone.By the optimization of the reaction conditions,a stable and better synthetic process route was obtained.The yield of terbutaline-D_(9)was 23.3%based on the consumed t-butylamine-D_(9).The targeted product was characterized by NMR,HPLC and HR-MS.Its chemical purity was 98.5%,and isotopic abundance was 98.4 atom%D.The prepared terbutaline-D_(9)can be used as an internal standard reagent for the determination of residual terbutaline of meat.