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Synthesis and characterization of d 5 ‐barbarin for use in barbarin‐related research
Author(s) -
Kudrimoti Sucheta,
Machin Jacob,
Arojojoye Adedamola S.,
Awuah Samuel G.,
Eisenberg Rodney,
Fenger Clara,
Maylin George,
Lehner Andreas F.,
Tobin Thomas
Publication year - 2023
Publication title -
drug testing and analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 54
eISSN - 1942-7611
pISSN - 1942-7603
DOI - 10.1002/dta.3357
Subject(s) - characterization (materials science) , nanotechnology , materials science
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 5 ‐barbarin to facilitate research on the relationship between plant barbarin and such aminorex identifications. D 5 ‐barbarin synthesis commenced with production of d 5 ‐2‐oxo‐2‐phenylacetaldehyde oxime ( d 5 ‐oxime) from d 5 ‐acetophenone via butylnitrite in an ethoxide/ethanol solution. This d 5 ‐oxime was then reduced with lithium aluminum hydride (LiAlH 4 ) to produce the corresponding d 5 ‐2‐amino‐1‐phenylethan‐1‐ol ( d 5 ‐ phenylethanolamine). Final ring closure of the d 5 ‐phenylethanolamine was performed by the addition of carbon disulfide (CS 2 ) 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 5 ‐barbarin as the product. Further characterization by high resolution mass spectrometry supports the successful synthesis of d 5 ‐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 5 ‐barbarin for use as an internal standard in barbarin‐related and equine forensic research.

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