SYNTHESIS OF ¹¹C -OHMEFENTANYL,A NEW,HIGHLY POTENT AND SELECTIVE AGONIST FOR OPIATE μ-RECEPTOR

Ohmefentanyl I is a new,highly potent and selective agonist for opiate μ-recptor. In order to visualize the μ-receptor by Positron Emission Tomography(PET),I labelcd with carbon-11 was synthesized using OH-precursor II or keto-precursor III.The OH-precursor Il was obtained by hydrolysis of cis-A-ohmefentanyl in 6 mol/L hydrochloric acid and the keto-precursor III was prepared by hydrolysis of cis-IV in 8 mol/L hydrochloric acid.The active intermediate¹¹C-propionyl chloride was prepared by the reaction between Grignard reagent ethylmagnesium bromide and cyclotron-produced¹¹C-carbon dioxide,followed by direct treatment of the radio-complex with phthaloyldichloride and 2,6-di-t-butylpyridine. Reaction of the OH-precursor Il with¹¹C-propionyl chlorideorreaction of the keto-precursor IIl with¹¹C-propionyl chloride and treatment with sodiumborohydride followed by HPLC separation all afforded¹¹C-ohmefentanyl with high specific activityof ll.1～14.8 GBq/μmol(300～400 mCi/μmo1)at 45～50 minutes after the end of bombardment(EOB).