An improved method for the synthesis of radiolabeled McN5652 via thioester precursors

• Published in: Nuclear medicine and biology Vol. 22; no. 4; pp. 543 - 545
• Main Authors: Suehiro, Makiko, Musachio, John L., Dannals, Robert F., Mathews, William B., Ravert, Hayden T., Scheffel, Ursula, Wagner, Henry N.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01-05-1995; Elsevier
• Subjects: Biological and medical sciences; Carbon Radioisotopes; Chromatography, High Pressure Liquid; Contrast media. Radiopharmaceuticals; Indicators and Reagents; Isoquinolines; Isotope Labeling - methods; Magnetic Resonance Spectroscopy; Medical sciences; Molecular Structure; Pharmacology. Drug treatments; Serotonin Antagonists; Tritium; Radiolabelling; Thioester; Radiochemistry; Isoquinoline; Technique; Pharmacokinetics; Chemical synthesis; Carbon; Precursor
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/0969-8051(94)00114-Y

An improved procedure that facilitates routine production and increases the radiochemical yield of [
11C]McN5652 (
trans — 1,2,3,5,6,10b-hexahydro-6-[4-([
11C]methylthio)-phenyl]pyrrolo-[2,1-
a]-isoquinoline) is presented. Specifically, thiol acetate, butyrate, and benzoate derivatives of McN5652 were prepared as the precursors for the [
11C]McN5652 synthesis. These thioesters offer greater stability than the previously used thiol precursor (desmethyl McN5652) and enable a single batch of material to be used for multiple radiolabelings. Hydrolysis of the thioester functionality (tetrabutylammonium hydroxide, 10 min) unmasked the free thiol which, without purification, was reacted with [
11C]iodomethane in DMF at 40–45 °C for 1 min. The average decay-corrected radiochemical yield for [
11C]McN5652 was 26% with an average specific activity of 2290mCi/μmol (end of synthesis). This facile radiolabeling method, utilizing the butyrate thioester of McN5652, was also employed in the preparation of [
3H](+)- and (−)McN5652 [
trans-1,2,3,5,6
S (or 6
R),10
bR, (or 10
bS)-hexahydro-6-[4-([
3H]methylthio)phenyl] pyrrolo-[2,1,
a]-iso-quinoline] from [
3H]iodomethane.