放射性同位素氢标记血根碱全合成研究

The Total Synthesis of Radioisotope Hydrogen-3 Labelled Sanguinarine

关键词:  饲用禁抗  博落回提取物  血根碱  全合成  放射性同位素示踪技术  

Key words:  Prohibiting the addition of antibiotics in feed  Macleaya cordata extract  Sanguinarine  Total synthesis  Radio isotope tracer technique.

摘要:

在饲用禁抗背景下，以血根碱为主要活性成分开发的国家二类新兽药博落回提取物作为抗生素替代品逐渐投入到养殖生产中，也同时面临长期使用潜在的食品安全风险。基于此，我们首次开展了放射性同位素[3H]标记血根碱的全合成。以[3H]碘甲烷为放射性同位素源，通过甲基化、氧化脱氢和还原酸化等反应制备得到放射性同位素3H标记的血根碱，其结构经薄层色谱和高效液相色谱—串联四级杆质谱联用仪分析确认，反应总化学收率和放化收率36%和82%。经高效液体相色谱和ARC流式液体闪烁计数仪测定表明，标记物的化学纯度和放化纯度均大于97%，比活度为4 mCi/mg，十二个月内质量稳定。该标记物可作为放射性示踪剂，用于血根碱的代谢、残留和消除等研究。

Abstract:

Under the background of prohibiting the addition of antibiotics in feed, the Macleaya cordata extract, a new national class II veterinary drug developed with sanguinarine as the main active ingredient, has been gradually put into breeding production as an antibiotic alternative, and at the same time, it faces potential food safety risks for long-term use. Herin, we carried out the first total synthesis of radioisotope [3H]-labeled sanguinarine. Using [3H]-iodomethane as the radioisotope source, the radioisotope [3H]-labeled sanguinarine was prepared through the reactions of methylation, oxidative dehydrogenation, and reductive acidification, and its structure was identified by thin-layer chromatography and high-performance liquid chromatography-tandem quadrupole mass spectrometry. The total chemical yield and radiochemical yield were 36% and 82%, respectively. Measurements by high-performance liquid chromatography and ARC flow-through liquid scintillation counter showed that the chemical and putative purity of the marker was greater than 97%, with a specific activity of 4 mCi/mg, and that the quality of the marker was stable over a twelve-month period. The marker can be used as a radioactive tracer for the study of metabolism, residue and elimination of sanguinarine.