Enantioselective synthesis of carbon-11 labeled L-alanine using phase transfer catalysis of Schiff bases

Radiolabeled amino acids are an important class of compounds that can be used for Positron Emission Tomography (PET) imaging of the amino acid transporter status of various diseases e.g., cancer. Current radiochemistry techniques do not offer synthesis approaches that are generally applicable and result in high yields and enantiomeric purity. Here, the radiosynthesis of l-[11C]alanine is described employing an enantioselective alkylation of a Schiff base glycine precursor with [11C]methyl iodide. By conducting a comprehensive reaction conditions optimization and a strategic analysis of several phase-transfer catalysts that facilitate enantioselective alkylation, the radiosynthesis of l-[11C]alanine was achieved in good radiochemical conversion, short reaction times and above 90% enantiomeric excess. This new methodology is broadly applicable and could also be used for the radiolabeling of other amino acids with carbon-11.