Fluorosugars: synthesis of the 2,3,4-trideoxy-2,3,4-trifluoro hexose analogues of d-glucose and d-altrose and assessment of their erythrocyte transmembrane transport

Abstract

The 2,3,4-trideoxy-2,3,4-trifluoro hexose analogues of d-glucose and d-altrose were prepared and characterised and these novel sugar analogues were explored by 2D-(19)F-EXSY NMR for their potential to cross erythrocyte (red blood cell) membranes, by comparison with the well known capacity of erythrocytes to transport d-glucose.

Investigating the Influence of (Deoxy)fluorination on the Lipophilicity of Non‐UV‐Active Fluorinated Alkanols and Carbohydrates by a New log P Determination Method

“…Interestingly,2 ,3-dideoxymonofluorinated 51 is much more hydrophilic.T he change from 51 to 52 represents CHÀHf or CH À Freplacement, and this is only the second example here with alog P increase for such achange.Afurther increase by one log P unit is achieved by trideoxyfluorination as in 2,3,4-trideoxy-2,3,4-trifluoroglucose 55. [23] Interestingly,t his 10 3 fold increase in the P value can also be achieved by mere dideoxygenation if the individual CHOH groups are both replaced by CF 2 groups (as in 53, 54). Fort hese sugar derivatives,t he relative configuration of the remaining CHOH group also strongly impacts on the lipophilicity.…”

Transmembrane exchange of fluorosugars: characterization of red cell GLUT1 kinetics using 19F NMR

“…Nevertheless, it may play a role in the reduction of α-tocopherol in the cell membrane (45). We surmise that the primary role of ascorbate in the Glc-free media (21,28,29) is to spontaneously transfer electrons to oxidized glutathione and NAD. In turn, NADH transfers electrons to Fe(III) in methemoglobin thus keeping most of the hemoglobin in the RBCs in a diamagnetic state; this is optimal for the signal-to-noise and resolution in NMR spectra.…”

“…In order to assess the stability of RBCs in the medium, we used 1 H spin-echo NMR experiments (27) to monitor ongoing production of lactate from glycolysis by RBCs in four different media: (I) 'normal' saline (150 mM NaCl + 10 mM KCl); (II) 'normal' saline with addition of 10 mM Glc; (III) the 'standard' ascorbate saline that was used in some previous 19 F-NMR studies of fluorosugars with RBCs (21,28,29); and (IV) the developed inosine saline. The 1 H spin-echo NMR spectra of each medium were recorded for 5 min (using spin-echo delay = 67 ms) in 1-hour intervals; the obtained spectra are shown as stacked plots in Fig.…”

“…The energy is largely dissipated in the re- (42). The use of 5 mM ascorbic acid (vitamin C; ascorbate at physiological pH) in Tris-HEPESbuffered saline has also been used as a medium for fluorosugar NMR experiments (21,28,29). However, this is not optimal, because ascorbate, if oxidized by dissolved O 2 , is converted to dehydroascorbate (DHA), which is known to be transported via GLUT1 (43,44).…”

The Synthesis of η‐1,2,3,4,5,6‐Hexafluorocyclohexane (Benzene Hexafluoride) from Benzene

“…A more informative spectrum was revealed at −70 °C (CD 2 Cl 2 ) where the ring interconversion is slowed sufficiently such that all of the six fluorine atoms of 3 a are resolved (Figure 4 B). The individual signals were assigned by 19 F NMR 2D‐EXSY correlation spectroscopy 14. 15 This analysis reveals that the two 1,3‐diaxial CF bonds show a large through‐space coupling ( 4 J HF =30.6 Hz) confirming their close proximity in space.…”