Synthesis and characterization of barbarin, a possible source of unexplained aminorex identifications in forensic science

Abstract

Aminorex is a US DEA Schedule 1 controlled substance occasionally detected in racing horses. A number of aminorex identifications in sport horses were thought to have been caused by exposure to plant sources of aminorex. Glucobarbarin, found in plants of the Brassicaceae family, has been suggested as a potential proximate chemi

Synthesis and characterization of d5‐barbarin for use in barbarin‐related research

“…This oxime product was obtained in good yield and reduced with lithium aluminum hydride, 11 producing the corresponding d 5 ‐ phenylethanolamine, again in good yield. Final ring closure of the d 5 ‐ phenylethanolamine was performed by addition of carbon disulfide in the presence of pyridine, as previously described 13,14 . The d 5 ‐barbarin reaction product was presented as a stable white crystalline powder, which was obtained in sufficient yield, purified by recrystallization, and chemically characterized as d 5 ‐barbarin by proton NMR, HPLC, and ESI‐mass spectrometry and prepared for use as an internal standard in barbarin‐related research.…”

“…Reduction of d 5 ‐oxime using LiAlH 4 afforded the hydroxyamine, d 5 ‐2‐amino‐1‐phenylethan‐1‐ol ( d 5 ‐ phenylethanolamine). The final ring closure step to form d 5 ‐barbarin is an atom‐economy transformation that utilizes carbon disulfide in pyridine as described in our previous reports on the synthesis of unlabeled barbarin 13,14 . Details on the synthesis are provided in the supporting information.…”

“…Final ring closure of the d 5 -phenylethanolamine was performed by addition of carbon disulfide in the presence of pyridine, as previously described. 13,14 The d 5 -barbarin reaction product was presented as a stable white crystalline powder, which was obtained in sufficient yield, purified by recrystallization, and chemically characterized as…”

“…To address this matter, we have streamlined the synthesis, purified, and characterized d 5 -barbarin, the availability of which will allow more definitive identification of the relationship between plant barbarin and equine consumption of such plant material being associated with equine aminorex identifications. D 5 -barbarin was synthesized by a variant of previously described barbarin synthesis methods [10][11][12][13][14] as follows. our previous reports on the synthesis of unlabeled barbarin.…”

“…our previous reports on the synthesis of unlabeled barbarin. 13,14 Details on the synthesis are provided in the supporting information. and mass spectrometry as appropriate for d 5 -oxime, m/z 154.0791, 1 HNMR (DMSO-d 6 , 400 MHz) δ (ppm): 1 H (s, 8.0, 1H), as in Figure S1 in the supporting information.…”