The Department of Veterinary Science and the Maxwell H. Gluck Equine Research Center and the Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, Kentucky, USA.
Department of Chemistry, University of Kentucky, Lexington, Kentucky, USA.
Drug Test Anal. 2023 Jan;15(1):42-46. doi: 10.1002/dta.3357. Epub 2022 Aug 23.
Based on structural similarities and equine administration experiments, Barbarin, 5-phenyl-2-oxazolidinethione from Brassicaceae plants, is a possible source of equine urinary identifications of aminorex, (R,S)-5-phenyl-4,5-dihydro-1,3-oxazol-2-amine, an amphetamine-related US Drug Enforcement Administration (DEA) controlled substance considered illegal in sport horses. We now report the synthesis and certification of d -barbarin to facilitate research on the relationship between plant barbarin and such aminorex identifications. D -barbarin synthesis commenced with production of d -2-oxo-2-phenylacetaldehyde oxime (d -oxime) from d -acetophenone via butylnitrite in an ethoxide/ethanol solution. This d -oxime was then reduced with lithium aluminum hydride (LiAlH ) to produce the corresponding d -2-amino-1-phenylethan-1-ol (d -phenylethanolamine). Final ring closure of the d -phenylethanolamine was performed by the addition of carbon disulfide (CS ) with pyridine. The reaction product was purified by recrystallization and presented as a stable white crystalline powder. Proton NMR spectroscopy revealed a triplet at 5.88 ppm for one proton, a double doublet at 3.71 ppm for one proton, and double doublet at 4.11 ppm for one proton, confirming d -barbarin as the product. Further characterization by high resolution mass spectrometry supports the successful synthesis of d -barbarin. Purity of the recrystallized product was ascertained by High Performance Liquid Chromatography (HPLC) to be greater than 98%. Together, we have developed the synthesis and full characterization of d -barbarin for use as an internal standard in barbarin-related and equine forensic research.
基于结构相似性和马属动物管理实验，来自十字花科植物的 5-苯基-2-恶唑烷硫酮，是马属动物尿液中鉴定出的苯丙醇胺（（R，S）-5-苯基-4,5-二氢-1,3-恶唑-2-胺）的可能来源，苯丙醇胺是一种与安非他命有关的美国缉毒局（DEA）管制物质，在运动马中被视为非法。我们现在报告 d-巴伯林的合成和认证，以促进对植物巴伯林与这种苯丙醇胺鉴定之间关系的研究。d-巴伯林的合成始于通过正丁基亚硝酸酯在乙氧基/乙醇溶液中从 d-苯乙酮生产 d-2-氧代-2-苯乙酰胺肟（d-肟）。然后，该 d-肟用氢化铝锂（LiAlH）还原生成相应的 d-2-氨基-1-苯乙醇-1-醇（d-苯乙醇胺）。最后，通过在吡啶中添加二硫化碳（CS）完成 d-苯乙醇胺的环闭合。反应产物通过重结晶进行纯化，并呈现为稳定的白色结晶粉末。质子 NMR 光谱显示 5.88ppm 处有一个质子的三重峰，3.71ppm 处有一个质子的双峰，4.11ppm 处有一个质子的双峰，证实 d-巴伯林是产物。高分辨率质谱进一步表征支持 d-巴伯林的成功合成。通过高效液相色谱法（HPLC）确定重结晶产物的纯度大于 98%。总之，我们已经开发出 d-巴伯林的合成和全面表征，可作为与巴伯林相关和马法医研究中内标的使用。
