Chemoenzymatic n.c.a synthesis of the coenzyme UDP‐2‐deoxy‐2‐[¹⁸F]fluoro‐α‐D‐glucopyranose as substrate of glycosyltransferases

The development of 18 F‐labelling methods adopted to proteins and bioactive peptides is of great interest in radiopharmaceutical sciences. In order to provide 18 F‐labelled sugars as a polar prosthetic group for an enzymatic 18 F‐labelling procedure, an appropriate nucleotide activated sugar is needed. Here, we present the radiosynthesis of n.c.a. UDP‐2‐deoxy‐2‐[ 18 F]fluoro‐α‐D‐glucopyranose (UDP‐[ 18 F]FDG) as a substrate for glycosyltransferases. The MacDonald synthesis of [ 18 F]FDG‐1‐phosphate was successfully combined with an enzymatic activation to obtain UDP‐[ 18 F]FDG directly in an aqueous medium located in the void volume of a solid phase cartridge. The radiochemical yield of UDP‐[ 18 F]FDG was 20% (based on [ 18 F]fluoride) after a total synthesis time of 110 min. Thus, an intermediate was provided for the enzymatic transfer of [ 18 F]FDG using UDP‐[ 18 F]FDG as glycosyl donor making use of a suitable glycosyltransferase. This would represent a highly selective and mild 18 F‐labelling method for glycosylated biomolecules.