Synthesis, Characterization, and Metabolism Studies of Fluspidine Enantiomers

The enantiomers of the potent σ₁ ligand fluspidine (1) were prepared by using chiral preparative HPLC. Synthesis of racemic tosylate 2 and subsequent separation of enantiomers yielded (R)-2 and (S)-2 in excellent enantiomeric purities. The fluspidine enantiomers (R)-1 and (S)-1 were synthesized from (R)-2 and (S)-2 by nucleophilic substitution with tetra-n-butyl-ammonium fluoride, affording (R)-1 with 99.6% ee and (S)-1 with 96.4% ee. Tosylates (R)-2 and (S)-2 can also serve as precursors for the radiosynthesis of enantiomerically pure radiotracers ¹⁸F](R)-1 and [¹⁸F-1.