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

Abstract

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. Copyright © 2001 John Wiley & Sons, Ltd.