4-Nitrophenyl activated esters are superior synthons for indirect radiofluorination of biomolecules.

Indirect radiolabelling has for a long time been the mainstay strategy for radiofluorination of biomolecules. Acylation of biomolecules through the use of an ¹⁸ F-labelled activated ester is a standard method for indirect radiolabelling. However, the preparation of ¹⁸ F-labelled activated esters is typically a complex and multistep procedure. Herein, we describe the use of 4-nitrophenyl (PNP) activated esters to rapidly prepare ¹⁸ F-labelled acylation synthons in one step. Furthermore, we present a comparative study of PNP activated esters and the commonly utilised 2,3,5,6-tetrafluorphenyl (TFP) activated esters under direct radiofluorination conditions and demonstrate their relative acylation behaviour. We demonstrate the superiority of PNP esters under direct radiofluorination conditions with favourable acylation kinetics.
(This journal is © The Royal Society of Chemistry 2020.)