Synthesis and Purification of DTBZ Precursors

Syntheses of the precursor to 9-(+)-¹¹C-DTBZ were purchased from ABX. The precursor of 10-(+)-¹¹C-DTBZ was synthesized according to Freyberg et al and can yield this precursor after hydrolysis [29 (link)]. (+)-DTBZ was prepared by reducing and demethylating tetrabenazine (TBZ) to obtain (+)-9-O-desmethyl-DTBZ or (+)-10-O-desmethyl-DTBZ. TBZ derivatives (Fig 1) were synthesized in the laboratory of the School of Pharmacy (National Taiwan University, Taipei, Taiwan). Sodium hydroxide was purchased from Sigma-Aldrich (St. Louis, MO, USA). Trifluoroacetic acid was purchased from Alfa Aesar (Ward Hill, MA, USA). Analytical reagent-grade reagents and solvents were purchased from Aldrich or Merck. The tC₁₈ Sep-Pak and Sep-Pak Light QMA cartridges were acquired from Waters Chromatography Division, Millipore Corporation.
HPLC analysis was performed with a Waters HPLC system equipped with both UV (280 nm) and radioactivity detectors.