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Synthesis of a novel fluorinated phosphonyl C-glycoside, (3-deoxy-3-fluoro- F β-d-glucopyranosyl)methylphosphonate, a potential inhibitor of β- phosphoglucomutase Postprint

Date

2023

Authors

Carroll-Poehls, Madison
Jakeman, David L.

Journal Title

Journal ISSN

Volume Title

Publisher

Elsevier

Abstract

β-phosphoglucomutase (βPGM) catalyzes the conversion of β-glucose 1-phosphate (βG1P) to glucose-6-phosphate (G6P), a universal source of cellular energy, in a two-step process. Transition state analogue (TSA) complexes formed from substrate analogues and a metal fluoride (MgF3 and AlF4-) enable analysis of each of these enzymatic steps independently. Novel substrate analogues incorporating fluorine offer opportunities to interrogate the enzyme mechanism using 19F NMR spectroscopy. Herein, the synthesis of a novel fluorinated phosphonyl C-glycoside (3-deoxy-3-fluoro-β-D-glucopyranosyl)methylphosphonate (1), in 12 steps (0.85 % overall yield) is disclosed. A four-stage synthetic strategy was employed, involving: 1) fluorine addition to the monosaccharide, 2) selective anomeric deprotection, 3) phosphonylation of the anomeric centre, and 4) global deprotection. Analysis of βPGM and 1 will be reported in due course.

Description

In Press, Journal Pre-proof, Available online 2 November 2023

Keywords

Citation

Published Version: Madison Carroll-Poehls, David L. Jakeman, Synthesis of a novel fluorinated phosphonyl C-glycoside, (3-deoxy-3-fluoro-β-d-glucopyranosyl)methylphosphonate, a potential inhibitor of β-phosphoglucomutase, Carbohydrate Research, 2023, 108979, ISSN 0008-6215, https://doi.org/10.1016/j.carres.2023.108979

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