Institute of Organic Chemistry, University of Vienna, Währinger Straße 38, 1090, Vienna, Austria.
Vienna Doctoral School in Chemistry (DoSChem), University of Vienna, Währinger Straße 42, 1090, Vienna, Austria.
Chemistry. 2023 Nov 8;29(62):e202302277. doi: 10.1002/chem.202302277. Epub 2023 Sep 28.
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.
氟化碳水化合物是理解代谢通量和途径失调的重要工具。在糖支架的特定位置氟化可以导致增强的代谢稳定性和随后在细胞中的代谢捕获。然而，这一原则从未应用于研究戊糖磷酸途径 (PPP) 中稀有糖的代谢。在这项研究中，设计并合成了两种 d-景天庚酮糖的氟化衍生物：4-脱氧-4-氟-d-景天庚酮糖 (4DFS) 和 3-脱氧-3-氟-d-景天庚酮糖 (3DFS)。两种糖都被人成纤维细胞摄取，但只有 4DFS 被磷酸化。d-景天庚酮糖在 C-4 位的氟化有效地阻止了转醛醇酶和转酮醇酶的酶促降解。因此，4DFS 作为一种新的 PPP 成像探针具有很高的潜力，基于代谢捕获的原理。因此，提出了用于未来用氟-18 进行放射性氟化的 4DFS 的潜在放射性标记前体的合成。
