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

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

Organisation(s)
Department of Organic Chemistry, Department of Analytical Chemistry, NMR Centre, Department of Inorganic Chemistry
External organisation(s)
Medizinische Universität Wien, Vienna Doctoral School in Chemistry (DoSChem), Ludwig Boltzmann Intitute Applied Diagnostics
Journal
Chemistry - A European Journal
Volume
29
ISSN
0947-6539
DOI
https://doi.org/10.1002/chem.202302277
Publication date
11-2023
Peer reviewed
Yes
Austrian Fields of Science 2012
104015 Organic chemistry
Keywords
ASJC Scopus subject areas
Catalysis, General Chemistry, Organic Chemistry
Portal url
https://ucrisportal.univie.ac.at/en/publications/5a586c1f-005b-4d4f-a7eb-0b5b5f7f4231