Synthesis of 4-Deoxy-4-Fluoro-D-Sedoheptulose: A Promising New Sugar to Apply the Principle of Metabolic Trapping

Fluorinated carbohydrates are important tools for understanding the deregulation of metabolic fluxes and pathways. Fluorinating specific positions within the sugar scaffold can lead to enhanced metabolic stability and subsequent metabolic trapping in cells. This principle has, however, never been applied to study the metabolism of the rare sugars of the pentose phosphate pathway (PPP). In this study, two fluorinated derivatives of d-sedoheptulose were designed and synthesized: 4-deoxy-4-fluoro-d-sedoheptulose (4DFS) and 3-deoxy-3-fluoro-d-sedoheptulose (3DFS). Both sugars are taken up by human fibroblasts but only 4DFS is phosphorylated. Fluorination of d-sedoheptulose at C-4 effectively halts the enzymatic degradation by transaldolase and transketolase. 4DFS thus has a high potential as a new PPP imaging probe based on the principle of metabolic trapping. Therefore, the synthesis of potential radiolabeling precursors for 4DFS for future radiofluorinations with fluorine-18 is presented.

Automated summary

Fluorinated carbohydrates are valuable tools for studying metabolic pathways, and this study explores their potential in investigating the metabolism of rare sugars in the pentose phosphate pathway (PPP). Two fluorinated derivatives of d-sedoheptulose were synthesized, with 4DFS showing potential as a new PPP imaging probe.