Synthesis of the dopamine D2/D3 receptor agonist (+)-PHNO via supercritical fluid chromatography: preliminary PET imaging study with [3-11C]-(+)PHNO

Abstract Carbon-11 labeled (+)-4-[1- 11 C]propyl-3,4,4 a ,5,6,10 b -hexahydro-2 H -naphtho[1,2- b ][1,4]oxazin-9-ol ([1- 11 C]-(+)-PHNO) is a dopamine D 3 -preferring agonist radiopharmaceutical used for medical imaging by positron emission tomography (PET). We report the synthesis of (+)-PHNO using supercritical fluid chromatography for enantiomeric resolution of its norpropyl derivative, HNO, followed by propylation. (+)-HNO was used to prepare the radiolabeling precursor, (+)- trans -4-acetyl-9-triisopropylsilyloxy-2,3,4 a ,5,6,10 b -hexahydro-4 H -naphth[1,2 b ][1,4]oxazine, in 12 steps. Modifications to the labeling procedure were made to ensure consistent preparation of [3- 11 C]-(+)-PHNO via [ 11 C]CH 3 I. A preliminary PET imaging study was carried out with this tracer in an attempt to image dopamine receptors in brown adipose tissue (brown fat) in vivo.