18F-Fluorination of 2-methyl-6-nitrobenzenesulfonate ester and its application to the synthesis of a 18F-labeled amino acid.

In the development of an efficient 18F-labeling method for the synthesis of PET tracers, it is essential not only to improve the efficiency of [18F]fluorine incorporation into a carrier but also to minimize non-radioactive side products from the precursor. Highly reactive sulfonate esters are promising precursors for 18F-nucleophilic fluorination under mild conditions. However, the expected labeling efficiency from the precursor is often hampered by its competitive degradation due to coexisting bases during 18F-fluorination. In this report, we designed a 2-methyl-6-nitrobenzenesulfonate (2-MeNs) ester as a precursor for 18F-fluorination, in which the methyl group suppresses hydrolysis of the sulfonate ester via steric hindrance. An increase in labeling efficiency in the 18F-labeling of a neopentyl labeling group was observed for the neopentyl 2-MeNs ester compared with that of the 2-nitrobenzenesulfonate ester. Ultimately, we achieved the automated synthesis of an 18F-labeled amino acid using a neopentyl labeling group by using a 2-MeNs ester as a precursor.