Study of the Impact of Fluorine Atom on the Glycosylation of Unprotected Furanosyl Acceptor

PS2 Poster session 2 Even numbers
Location (hall): 
Start/end time: 
Tuesday, July 2, 2019 - 15:45 to 17:15

Jeane Vaugenot1, Vincent Ferrières1, Thierry Benvegnu1

1Univ Rennes, Ecole Nationale Supérieure de Chimie de Rennes,  CNRS, ISCR-UMR 6226, Rennes , France

Carbohydrates are well represented in nature, in particular in biological mechanisms. Unlike pyranoses, furanoses are absent from mammals (except in the DNA) but they can be found in cell wall bacteria, fungi and parasitic microorganisms.[1,2] This explains why they are an interesting target for the development of new bioactive agents.

Enzymatically synthesized fluorinated on the C-6 position octyl di-Galf showed interesting biological properties, in particular on macrophages and dendritic cells.[3,4] Fluorine is more and more used in pharmaceuticals products because it can substitute H or OH group with minimal steric perturbation.[5–7] Nevertheless its electronegativity can change the reactivity of the molecule.

In order to pursue the tests on these compounds, bigger amount of product was required and the enzymatic synthesis could not afford them. We expected that the presence of fluorine at primary position could induce discrimination of the hydroxyl reactivity. Therefore, direct glycosylation reactions were attempted on an acceptor with free 2, 3, 5-OH. Selectivity of the glycosylation reaction with two different donors (thiophenyl and brominated) was studied. It led to the production of three disaccharides on all the possible positions but also the synthesis of trisaccharide branched on O-2 and O-3. More surprisingly, ring expansion and the synthesis of a transglycosylation product were observed. The latest resulted on the striking transfer of the aglycon from the acceptor (octyl chain) on the donor.

Experimental evidences will be presented to rationalize this side reaction observed for the first time from O- and S-glycosides.

Isolated compounds following the glycosylation reactions

  1. Peltier P, Euzen R, Daniellou R, Nugier-Chauvin C, Ferrières V. Recent knowledge and innovations related to hexofuranosides: structure, synthesis and applications. Carbohydr Res. 2008 Aug;343(12):1897–923. 
  2. Dureau R, Robert-Gangneux F, Gangneux J-P, Nugier-Chauvin C, Legentil L, Daniellou R, et al. Synthetic UDP-furanoses inhibit the growth of the parasite Leishmania. Carbohydr Res. 2010 Jul;345(10):1299–305. 
  3. Chlubnová I, Filipp D, Spiwok V, Dvořáková H, Daniellou R, Nugier-Chauvin C, et al. Enzymatic synthesis of oligo-d-galactofuranosides and l-arabinofuranosides: from molecular dynamics to immunological assays. Org Biomol Chem. 2010;8(9):2092. 
  4. Chlubnová I, Králová B, Dvořáková H, Spiwok V, Filipp D, Nugier-Chauvin C, et al. Biocatalyzed synthesis of difuranosides and their ability to trigger production of TNF-α. Bioorg Med Chem Lett. 2016 Mar;26(6):1550–3. 
  5. Berger AA, Völler J-S, Budisa N, Koksch B. Deciphering the Fluorine Code—The Many Hats Fluorine Wears in a Protein Environment. Acc Chem Res. 2017 Sep 19;50(9):2093–103. 
  6. Cavaliere A, Probst KC, Westwell AD, Slusarczyk M. Fluorinated nucleosides as an important class of anticancer and antiviral agents. Future Med Chem. 2017 Oct;9(15):1809–33. 
  7. Purser S, Moore PR, Swallow S, Gouverneur V. Fluorine in medicinal chemistry. Chem Soc Rev. 2008;37(2):320–30.