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

Lukas Scheibelberger, Toda Stankovic, Marlene Pühringer, Hanspeter Kählig, Theresa Balber, Eva Maria Patronas, Evelyn Rampler, Markus Mitterhauser, Arvand Haschemi, Katharina Pallitsch (Corresponding author)

Publications: Contribution to journalArticlePeer Reviewed

Abstract

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.

Original languageEnglish
Article numbere202302277
JournalChemistry - A European Journal
Volume29
Issue number62
DOIs
Publication statusPublished - 8 Nov 2023

Austrian Fields of Science 2012

  • 104015 Organic chemistry

Keywords

  • d-sedoheptulose
  • fluorinated carbohydrates
  • metabolic trapping
  • pentose phosphate pathway
  • rare sugars

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