Abstract
The authors of the present paper reported the synthesis of [^11^C]‐ohmefentanyl in a symposium abstract in 1991^(1)^. We here describe the results of synthesis and analysis in detail. Ohmefentanyl 1 is a novel, highly potent and selective agonist for opiate μ‐receptors. In order to visualize the μ‐receptor by Positron Emission Tomography (PET), this compound was labelled with carbon‐11. The unlabelled cis‐A‐ohmefentanyl was prepared in a nine‐step synthesis and two‐step fractional crystallization, and the OH‐precursor 11 for [^11^C]‐ohmefentanyl labelling was obtained by hydrolysis of the 4‐N‐propionyl group of cis‐A‐ohmefentanyl in 6 N hydrochloric acid. The [^11^C]‐propionyl chloride was prepared by carbonation of ethylmagnesium bromide with cyclotron‐produced [^11^C]‐carbon dioxide followed by direct treatment of the intermediate complex with phthaloyl dichloride and 2,6‐di‐t‐butylpyridine. Reaction of the OH‐precursor 11 with [^11^C]‐propionyl chloride yields [^11^C]‐ohmefentanyl separated by HPLC, with a high specific activity of 11.1 – 14.8 GBq μmol^−1^ (300−400 mCi μmol^−1^), 49 minutes after the end of bombardment.
The keto‐precursor 12, prepared by hydrolysis of the 4‐N‐propionyl group of cis‐10 in 8 N hydrochloric acid, was also used for [^11^C]‐ohmefentanyl labelling. Reaction of the [^11^C]‐propionyl chloride with keto‐precursor 12, followed by addition of sodium borohydride, yields [^11^C]‐ohmefentanyl.
The [^11^C]‐labelled ohmefentanyl obtained using the OH‐precursor 11 is a cis‐A form, while that obtained using the keto‐precursor is a mixture of cis‐A and cis‐B forms.