Synthesis and carbon-11 labeling of (R)- and (S)-thionisoxetine, norepinephrine reuptake inhibitors, potential radioligands for positron emission tomography

Standards and des-methyl precursors of (R)- and (S)-thionisoxetine, potent and selective norepinephrine reuptake inhibitors, were synthesized and radiolabeled with carbon-11. Both enantiomers of the N-methyl-3-(2-thiomethylphenoxy)-3-phenylpropanamine and the 3-(2-thiomethylphenoxy)-3-phenylpropylamine were obtained via multi-step syntheses, while the radiosyntheses were carried out using [11C]CH3I. The radiochemical yields were 26%, decay corrected and the specific radioactivity ranging from 2 to 3 Ci/μmol. The HPLC analyses were performed using a chiral column: during the radiolabeling, no racemization occurred and the isomers were synthesized with high enantiomeric purity.