title: A rapid and highly enantioselective C-11C bond formation of l-[11C]phenylalanine via chiral phase-transfer catalysis.
abstract: A rapid method for the synthesis of carbon-11 radiolabeled phenylalanine was developed using a chiral phase-transfer catalyst and a sub-nanomolar quantity of [11C]benzyl iodide as a radio-precursor. Based on a reported synthesis of [11C]benzyl iodide, a Schiff base precursor was evaluated for stereoselective [11C]benzylation. Extensive and interactive screening of the precursor, catalyst, base, stirring and temperature was required to achieve high stereoinduction. The result is an efficient 5-step radiolabeling method to reliably synthesize l- or d-[11C]phenylalanine with an excellent enantiomeric excess of >90% and almost quantitative radiochemical conversion of >95% (n > 5). Additionally, a phase-transfer catalyzed alkylation was utilized on the preparative scale using automated platform. The application resulted in high specific activity ranging from 85-135 GBq μmol-1of the enantiomerically pure [11C]phenylalanine, showing that the process is robust and amenable to broad use in PET.
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands. a.pekosak@vumc.nl.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Pekošak
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands. a.pekosak@vumc.nl.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Filp
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands. a.pekosak@vumc.nl and Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Janja
authors.initials: J
authors.lastname: Škrinjar
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands. a.pekosak@vumc.nl.
authors.forename: Alex J
authors.initials: AJ
authors.lastname: Poot
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands. a.pekosak@vumc.nl.
authors.forename: Albert D
authors.initials: AD
authors.lastname: Windhorst
mesh_terms: D002250:Carbon Radioisotopes; D002384:Catalysis; D015394:Molecular Structure; D044367:Phase Transition; D010649:Phenylalanine / Q000138:chemical synthesis* / Q000737:chemistry; D049268:Positron-Emission Tomography; D013237:Stereoisomerism
chemical_list: D002250:Carbon Radioisotopes; D010649:Phenylalanine