A rapid and highly enantioselective C–11C bond formation of l-[11C]phenylalanine via chiral phase-transfer catalysis

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 [ C-11]benzyl iodide as a radio-precursor. Based on a reported synthesis of [C-11]benzyl iodide, a Schiff base precursor was evaluated for stereoselective [C-11]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)-[C-11]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 mu mol(-1) of the enantiomerically pure [C-11]phenylalanine, showing that the process is robust and amenable to broad use in PET.