Synthesis of 2,6-dideoxy-2-fluoro-6-[18F]-fluoro-β-D-glucopyranosyl fluoride (2,6FGF) as a potential imaging probe for glucocerebrosidase

Article abstract of DOI:10.1002/jlcr.466

We have previously synthesized 2-deoxy-2-[¹⁸F]-fluoro-β-mannosyl [¹⁸F]-fluoride and shown that it behaves as a mechanism-based inhibitor of Agrobacterium sp. β-glucosidase. In-vivo experiments indicate that this compound undergoes partial hydrolysis to produce 2-deoxy-2-fluoro-mannose, which can become phosphorylated and trapped within the cell. We now report the synthesis of another 2-fluoro glycoside which is ¹⁸F-labelled at the 6 position so that the label cannot be lost during such glycoside hydrolysis and which, further, cannot be phosphorylated. The mechanism-based glycosidase inhibitor 2,6-dideoxy-2-fluoro-6-[¹⁸F]-fluoro-β-D-glucopyranosyl fluoride (2,6FGF) was synthesized in 69% overall chemical yield and in 9% radiochemical yield (decay corrected) as a potential imaging probe for glycosidase.