Exploring the Chemistry of Non‐sticky Sugars: Synthesis of Polyfluorinated Carbohydrate Analogues of d‐Allopyranose

Abstract

There is a growing interest in the preparation of polyfluorinated carbohydrates. A limited number of fluorohexopyranosides have been used in biological investigations because of the synthetic challenge they present. Hence, we report the synthesis of fluorinated homodimer, fluorodisaccharides, C‐terminal fluoroglycopeptides, lipoic acid fluoroglycoconjugate and trifluoroallopyranoside derivatives functionalized at C‐6. Our strategy uses levoglucosan as inexpensive starting material and facilitates an approach to complex carbohydrate analogues with multiple C−F bonds. The challenge of our synthetic route centered around an efficient preparation of crucial 1,6‐anhydro‐2,4‐dideoxy‐difluoroglucopyranose and focused on achieving a difficult glycosylation of the trifluoroallopyranose donor. The results clearly highlight challenges related to the preparation of polyhalogenated complex organic molecules and pave the way to access novel medically relevant tools.

Addressing the Structural Complexity of Fluorinated Glucose Analogues: Insight into Lipophilicities and Solvation Effects

“…A vast amount of research has also been implemented for the biological investigations and physical properties of polyfluorinated glucose analogues . As part of our program related to the synthesis of fluorinated carbohydrates, we developed a flexible strategy that allowed us the synthesis of a range of fluorinated carbohydrate analogues, enabling the determination of their lipophilicity . In this work, we wish to report the first systematic investigation involving the synthetic pathways to generate all mono‐, di‐, and trifluorinated glucopyranose analogues at position C‐2, C‐3, C‐4, and C‐6 (Figure C), along with the determination of their corresponding lipophilicities (in the context of this study, the term fluoroglucose refers to deoxyfluoroglucose).…”

Bottom-up Chemoenzymatic Synthesis Towards Novel Fluorinated Cellulose-like Materials

“…Products were lyophilized using a Labconco FreeZone Benchtop freeze dryer. 1 H, 13 C, 31 P and 19 F NMR spectra were recorded on a Bruker Avance III 400 MHz and/or Bruker Avance Neo 600 MHz spectrometers at 298 K. Chemical shifts recorded in D2O are reported with respect to the solvent residual peak at 4.79 ppm in 1 H NMR. High resolution mass spectra were acquired in a Synapt G2-Si mass spectrometer (Waters, UK) using electrospray ionisation (positive or negative mode).…”

The Role of Fluorine in Glycomimetic Drug Design

“…1,2‐Dideoxy‐1,2‐difluorinated glucose was first reported as an improved ligand for glycogen phosphorylase, with an observed affinity that was higher than expected based on the cumulative increases afforded by the two mono‐deoxyfluoro derivatives [5a] . Subsequent studies have similarly reported on various di‐deoxyfluoro, [53f, 54] tri‐deoxyfluoro, [25a, 51, 53f, 55] and tetra‐deoxyfluoro [25a, 55b] glycomimetic derivatives with significantly enhanced affinities.…”